Abstract Summary:

• Cilta-cel significantly improved overall MRD-negativity rates compared to standard of care (SoC), with rates over three times higher in the intent-to-treat (ITT) set (62% vs 18%) and among MRD-evaluable patients (89% vs 38%) at the 10⁻⁵ threshold.
• At the 12-month mark, 44% of patients in the cilta-cel arm achieved MRD-negative complete response (≥CR) compared to 8% in the SoC arm, highlighting the rapid achievement of MRD negativity post-cilta-cel infusion.
• Sustained MRD-negativity rates were significantly higher with cilta-cel, with 40% in the ITT set achieving sustained MRD negativity compared to 6% with SoC.
• Median progression-free survival (PFS) was not reached in patients with MRD-negative ≥CR at 12 months in the cilta-cel arm, indicating a strong prognostic value for MRD negativity.
• The study underscores the benefit of cilta-cel in achieving deep and sustained MRD negativity in len-refractory multiple myeloma, even as early as the first relapse.

Abstract
Introduction: Cilta-cel is approved in the US and EU for the treatment (tx) of patients (pts) with len-refractory MM after ≥1 line based on the randomized, phase 3 CARTITUDE-4 trial (NCT04181827). At the first interim analysis (15.9-month [mo] median follow-up), cilta-cel significantly improved progression-free survival (PFS) vs SoC (hazard ratio [HR], 0.26 [protocol-specified weighted analysis]; P<0.0001). At the second interim analysis, overall survival (OS) was significantly improved with cilta-cel vs SoC (HR, 0.55; P=0.0009). MRD negativity is a prognostic marker of prolonged survival outcomes for pts with MM. We report MRD negativity, including overall and sustained MRD negativity, overall MRD-negative complete response or better (≥CR), and MRD-negative ≥CR at mo 12, from the prespecified second interim analysis of CARTITUDE-4.

Methods: Eligibility criteria were previously described. Pts were assigned 1:1 to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd]/daratumumab, pomalidomide, and dexamethasone [DPd]). Pts in the cilta-cel arm underwent apheresis, received bridging therapy (PVd/DPd), and then a single cilta-cel infusion (target dose, 0.75× 10⁶ CAR+ viable T cells/kg) 5–7 days (d) after the start of lymphodepletion. PFS was the primary endpoint; ≥CR rate, overall response rate, overall MRD-negativity rate, and OS were key secondary endpoints. MRD was assessed centrally via next-generation sequencing (clonoSEQ v2.0; Adaptive Biotechnologies). MRD was evaluated at d 56 post infusion in the cilta-cel arm; and in both arms at suspected ≥CR and at 6, 12, 18, and 24 mo post infusion (cilta-cel arm) or cycle 1 d 1 (SoC arm), as well as yearly until progression/start of subsequent therapy in pts in ≥CR. Sustained MRD negativity (10⁻⁵) was defined as confirmed MRD negativity ≥12 mo apart and without MRD positivity in between. Pts were evaluable for sustained MRD negativity if they achieved MRD negativity and had ≥1 evaluable MRD sample ≥12 mo after the first negative result or progressed/died/started subsequent tx <12 mo after the first negative result.

Results: 419 pts were randomized (intent-to-treat [ITT] set; cilta-cel, n=208; SoC, n=211); 176 pts in the cilta-cel arm received cilta-cel as study tx. As of May 1, 2024, median follow-up for the study was 33.6 mo. At the 10⁻⁵ threshold, 145 pts in the cilta-cel arm and 103 in the SoC arm were evaluable for MRD. MRD-negativity rates (10⁻⁵) in the ITT set and the MRD-evaluable subset were higher with cilta-cel vs SoC (ITT, 62% vs 18%; MRD evaluable, 89% vs 38%; both P<0.0001). Across subgroups, cilta-cel vs SoC consistently increased overall MRD-negativity rates (10⁻⁵). In the ITT set, 48% of the cilta-cel arm achieved MRD negativity (10⁻⁵) by d 56, with the MRD-negative rate rising to 60% by 6 mo post cilta-cel infusion. Overall MRD-negativity rates at the 10⁻⁶ threshold in the ITT set were higher with cilta-cel vs SoC (57% vs 9%; P<0.0001). In the cilta-cel arm, 119 (57%) pts vs 26 (12%) in the SoC arm achieved overall MRD-negative (10⁻⁵) ≥CR (P<0.0001). At the 12-mo MRD assessment, 92 (44%) pts in the cilta-cel arm vs 17 (8%) in the SoC arm (P<0.0001) had MRD-negative (10⁻⁵) ≥CR. In pts with MRD-negative (10⁻⁵) ≥CR at mo 12, median PFS was not reached (NR; 95% CI, not estimable [NE]–NE) with cilta-cel and 37.8 mo (95% CI, 25.0–NE) with SoC; median OS was NR (95% CI, NE–NE) and NR (95% CI, 37.8 mo–NE), respectively. Sustained MRD-negativity rates (10⁻⁵) in the ITT set were 40% in the cilta-cel arm vs 6% in the SoC arm (P<0.0001); among 110 and 26 evaluable pts for sustained MRD, sustained MRD-negativity rates were 75% vs 50% (P=0.0159). Among the 176 pts who received cilta-cel as study tx, overall MRD negativity at 10⁻⁵ was achieved by 129 (73%) pts (89% of 145 evaluable pts).

Conclusions: At 33.6-mo median follow-up in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates >3-fold in the ITT set, with pts achieving MRD negativity rapidly post cilta-cel. The prognostic value of MRD-negative ≥CR at mo 12 was shown, as median PFS was >3 years in pts with MRD-negative ≥CR at mo 12, regardless of tx. These data further underscore the benefit of cilta-cel, which led to significant >3-fold increases vs SoC in rates of MRD-negative ≥CR at any time and at mo 12, and sustained MRD negativity. Our MRD data demonstrate higher rates of deep and sustained MRD negativity achieved with cilta-cel vs SoC in tx of len-refractory MM as early as first relapse.

Abstract Summary:

• In the Phase 2 iMMagine-1 trial, anitocabtagene autoleucel (anito-cel) demonstrated a high overall response rate (ORR) of 95% in patients with relapsed/refractory multiple myeloma (RRMM), with a complete/stringent complete response (CR/sCR) rate of 62%.
• Minimal residual disease (MRD) negativity was achieved in 92% of evaluable patients, indicating deep responses.
• The estimated 6-month progression-free survival (PFS) and overall survival (OS) rates were 90% and 95%, respectively, with median PFS and OS not yet reached.
• Safety profile showed manageable adverse events: 84% experienced cytokine release syndrome (CRS), mostly Grade 1, with only one Grade 5 event; immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 9% of patients, all resolving without sequelae.
• The study reported no delayed neurotoxicity or other severe neurological events, and the treatment was deemed effective and manageable in a high-risk RRMM population.

Abstract
Background: Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is an autologous anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy with a novel D-domain binder under development for patients (pts) with relapsed and/or refractory multiple myeloma (RRMM). Results from the Phase 1 study in pts with RRMM who had ≥3 prior lines of therapy (LoT; 4L+; N=38) demonstrated an overall response rate (ORR) of 100%, a complete response (CR)/stringent CR (sCR) rate of 76%, and an estimated 24-month progression-free survival (PFS) rate of 56% (Frigault MJ, et al. ASH 2023). Initial results from the ongoing iMMagine-1 Phase 2 registrational trial (NCT05396885) are presented in this report.

Methods: Eligible triple-class–exposed pts ≥18 years with RRMM who progressed after ≥3 prior LoT with evidence of measurable disease, and were refractory to their last LoT, were enrolled. Following leukapheresis, optional bridging, and anito-cel manufacturing, pts received lymphodepletion chemotherapy (fludarabine 30 mg/m²/d and cyclophosphamide 300 mg/m²/d for 3 days) and a single infusion of anito-cel (target dose of 115×10⁶ CAR+ viable T cells). The primary endpoint of the study is to determine the efficacy of anito-cel, assessed by ORR (sCR, CR, very good partial response [VGPR], and partial response [PR]), as determined by an independent review committee. Efficacy outcomes were assessed using 2016 International Myeloma Working Group (IMWG) criteria, minimal residual disease (MRD) was assessed by next-generation sequencing (sensitivity threshold, 10^-5), toxicity was graded per Common Terminology Criteria for Adverse Events version 5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by the American Society for Transplantation and Cellular Therapy consensus criteria. This preliminary analysis of pts with ≥2 months of follow-up after anito-cel infusion reports investigator-assessed safety and efficacy outcomes.

Results: As of June 1, 2024, 58 pts had received anito-cel infusion under the final manufacturing process with ≥2 months of follow-up after infusion; median follow-up was 10.3 months (range, 2.0-17.8). Median age was 66 years (range, 38-77). Pts had received a median of 4 prior LoT (range, 3-8) with 26 pts (45%) having received only 3 prior LoT. Forty pts (69%) were triple-class refractory and 20 (34%) were penta-class refractory. Investigator-assessed ORR per IMWG criteria was 95% (55/58) with a CR/sCR rate of 62% (36/58). Of those evaluable for MRD testing (n=39), 36 (92%) achieved MRD negativity at least to the level of 10^-5. The Kaplan–Meier-estimated 6-month PFS and overall survival (OS) rates (95% CI) were 90% (77-96) and 95% (85-98), respectively; median PFS and OS have not yet been reached.

Any grade (Gr) CRS was observed in 49 pts (84%). Notably, 46 pts (79%) had either no CRS (n=9, 16%) or Gr 1 CRS (n=37, 64%). Additionally, Gr 2 CRS events occurred in 11 pts (19%), and 1 pt (2%) had a Gr 5 CRS event. The median time to CRS onset was 2 days (range, 1-17) with a median duration of 3 days (range, 1-9). Of note, 31 pts (53%) had no fever or CRS in the first 3 days of anito-cel.

Any Gr ICANS was observed in 5 pts (9%): 2 (3%) Gr 1, 2 (3%) Gr 2, and 1 (2%) Gr 3 events. Median time to ICANS onset was 5 days (range, 2-7) with a median duration of 6 days (range, 1-10); all cases resolved without sequelae. No delayed neurotoxicity, cranial nerve palsies, Guillain Barre syndrome, or Parkinsonian-like symptoms were observed. Cytopenias were the most common Gr ≥3 treatment-emergent adverse events (AEs); 36 pts (62%) had Gr ≥3 neutropenia, 15 (26%) had Gr ≥3 thrombocytopenia, and 15 (26%) had Gr ≥3 anemia. Three deaths occurred due to AEs (both related and unrelated; retroperitoneal hemorrhage, CRS, fungal infection).

Conclusions: Preliminary results from the first 58 pts in the Phase 2 iMMagine-1 trial demonstrate deep and durable efficacy and manageable safety in a high-risk 4L+ RRMM population including triple- and penta-class refractory disease. Notably, no delayed neurotoxicity, cranial nerve palsies, Guillain Barre syndrome, or Parkinsonian-like symptoms were observed in the Phase 1 study or in the Phase 2 iMMagine-1 study to date. Updated data with additional follow-up will be presented.

Abstract Summary:

• HBI0101, a novel anti-BCMA CART therapy, demonstrated a high overall response rate of 92% and a complete/stringent complete response rate of 55% in patients with relapsed/refractory multiple myeloma.
• The study included a high-risk population, with 87% being triple refractory and 38% penta-refractory, and 17% having received prior anti-BCMA therapy.
• The median progression-free survival was 11.6 months, and the median overall survival was not reached at a median follow-up of 12 months.
• Safety was manageable, with common grade 3-4 hematological toxicities and cytokine release syndrome occurring in 95% of patients, but no grade 4/5 CRS or treatment-related deaths.
• The results support the efficacy and safety of HBI0101 in a frailer, higher-risk population and highlight the potential for academic settings to produce CART therapies to meet increasing demand.

Abstract
BACKGROUND: Although anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy proved unprecedented efficacy in patients with relapsed/refractory (R/R) multiple myeloma (MM), its availability remains limited. HBI0101 is a novel second generation optimized anti-BCMA CART, that was developed in an academic setting. The phase I study evaluating HBI0101 (NCT04720313) demonstrated manageable safety and high efficacy. Here we present the updated results of the phases 1b/2 study evaluating the efficacy and safety of 84 patients with R/R MM receiving the recommended phase II target dose (RP2D).

METHODS: The patients enrolled had R/R MM with at least 3 prior lines of therapy, including a proteosome inhibitor, immune modulator (IMiD) and anti CD38 antibody. Inclusion criteria were relatively permissive as compared with other CART clinical trials, including thresholds of 30×10⁹/ml platelets, creatinine clearance of 20ml/min and performance status of 2 by ECOG scale. The RP2D was 800×10^6 CART cells.

RESULTS: Eighty-four patients with a median of 4 prior lines (range 3-13) were included in the analysis. Most patients (73/84, 87%) were triple refractory, 32/84 (38%) were penta-refractory and 14/84 (17%) had received prior anti-BCMA therapy, mostly belantamab mafodotin. Extra-medullary disease was evident in 22/84 (26%). Thirty three of 81 (41%) had high-risk cytogenetics (t(4:14)/t(14:16)/del17), and 61/81 (75%) including 1Q-gain. Nearly half of this cohort (48%) would not have met the inclusion criteria for the registrational trials of both approved anti-BCMA CART. The manufacturing success rate was 84/84 (100%), and all patients included were infused with the RP2D.

The overall response rate was 77/84 (92%) and the complete response (CR)/stringent CR rate was 46/84 (55%). The minimal residual disease negativity rate (10^-5 by flow-cytometry) was 62/84 (74%). At data cutoff, with a median follow-up of 12.0 months (95% CI: 8.8-14.6), the median progression-free survival was 11.6 months (95% CI: 8.6-14.6) and the median overall survival was not reached (NR) (95% CI: 19.6-NR).

Safety was manageable with grade 3-4 hematological toxicities common (anemia- 62%, thrombocytopenia- 42%, neutropenia- 99%). Cytokine release syndrome (CRS) occurred in 80/84 (95%), including 16 patients with grade 3 CRS (19%), but no cases of grade 4/5. Neurological toxicity (ICANS or other) was rare and mild (3 cases, all of grade 1-2). No irreversible organ toxicities or treatment related deaths occurred.

Updated results will be communicated at the presentation time.

CONCLUSION: HBI0101 BCMA CART results demonstrate high efficacy and manageable safety in a frailer and higher risk population as compared with the registrational studies with commercial products. This data not only supports further utilization of HBI0101 CART therapy, but also of CART production at an academic setting in general, ensuring a sufficient CART supply in the light of the increasing demand.

Abstract Summary:

• The study evaluated anti-BCMA/GPRC5D bispecific CAR T-cells in RRMM patients with EMD, establishing a maximum tolerated dose of 2.0×10⁶ CAR T-cells per kg.
• Hematological toxicity was the most common severe adverse event, occurring in all patients, while cytokine release syndrome was observed in 62.5% of patients, all at grade 1 or 2.
• The overall response rate was 100%, with 50% achieving complete response, although one patient experienced subsequent disease progression.
• The trial indicates potential efficacy of this bispecific CAR T-cell therapy in RRMM with EMD, but further research in larger trials is necessary to validate these findings.

Abstract
Background: Despite the promising outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating relapsed or refractory multiple myeloma (RRMM), addressing extramedullary disease (EMD) in this context remains a therapeutic challenge. This study aimed to evaluate the safety, efficacy, and activity of anti-BCMA/GPRC5D bispecific CAR T-cells in RRMM patients with EMD.

Methods: A Phase I, single-arm, open-label clinical trial was conducted at the Western Theater Command Hospital of the Chinese People’s Liberation Army. Eligible patients were RRMM adults aged 18-75 years with ECOG performance status 0-3 and EMD. Patients received escalating doses of anti-BCMA/GPRC5D bispecific CAR T-cells, starting at 1.0× 10⁶ CAR T-cells per kg. The primary endpoints were safety and efficacy, while secondary endpoints encompassed assessment of activity. Safety and activity analyses encompassed all patients who received the CAR T-cell product per protocol. The study protocol was approved by the institutional ethics committee (2024EC1-ky033).

Results: Between July 2023 and May 2024, nine patients with RRMM and EMD were enrolled and underwent leukapheresis. Three patients were subsequently excluded due to rapid disease progression. Six patients received the anti-BCMA/GPRC5D bispecific CAR T-cell infusion. With a median follow-up of 6.5 months (IQR 2–12), the median age was 58 years (IQR 48–67), and the cohort included three males (50%) and three females (50%). Genetic risk factors were present in three patients, undetected in two, and absent in one. The maximum tolerated dose was established as 2.0× 10⁶ CAR T-cells per kg. Hematological toxicity, excluding lymphopenia, was the most frequent grade 3 or higher adverse event (100%). Cytokine release syndrome (CRS) occurred in 62.5% of patients, all of which were grade 1 or 2. The overall response rate (ORR) among evaluable patients was 100%, with three patients (50%) achieving complete response (CR), including one with subsequent disease progression. One patient (17%) achieved very good partial response (VGPR), and two (33%) achieved partial response (PR), both of whom subsequently died due to disease progression.

Conclusion: The findings of this Phase I trial suggest that anti-BCMA/GPRC5D bispecific CAR T-cell therapy may represent a promising therapeutic option for patients with refractory and relapsed multiple myeloma complicated by extramedullary disease. Further investigation in larger, controlled trials is warranted to confirm these preliminary observations and refine treatment strategies.

Abstract Summary:

• In this phase II study, Ciltacabtagene Autoleucel (cilta-cel) was administered to patients with high-risk smoldering myeloma (HR-SMM) without prior induction therapy, marking the first use of CAR T-cell therapy in a precursor cancer setting.
• No dose-limiting toxicities (DLTs) were observed in the safety run-in cohort at both 0.5 and 0.75 x 10⁶ CAR-positive T-cells/kg doses, and the treatment was generally well-tolerated with expected transient hematologic toxicities.
• All patients experienced low-grade cytokine release syndrome (CRS), with no high-grade CRS, ICANS, or grade 3 or greater infections reported.
• CAR T-cells showed robust expansion and persistence, with all patients achieving minimal residual disease (MRD) negativity at 10⁻⁶ by day 28, and sustained MRD negativity with a 100% overall response rate and 50% complete response rate.
• The study suggests that cilta-cel could offer a safe and effective treatment option for HR-SMM, potentially altering future therapeutic strategies in multiple myeloma by eliminating the need for induction therapy.

Abstract
Introduction: CAR-T cell therapy has been used in relapsed multiple myeloma (MM) with deep and durable responses but some patients still eventually relapse. We hypothesized that the use of Ciltacabtagene Autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, can be safe and highly effective in patients with high-risk smoldering myeloma (HR-SMM), where the tumor burden is lower with less genomic complexity and the immune system is more fit, potentially leading to less toxicity and improved durable remissions in this high risk precursor condition. To our knowledge, this is the first study to examine the use of CAR T-cell therapy without any induction therapy in a precursor malignant condition.

Methods: This is a phase II, single arm study of cilta-cel in HR-SMM, defined per the Mayo/IMWG 20-2-20 model, IMWG risk score of 9 or greater, high-risk FISH, evolving pattern or the PETHEMA criteria. Patients with >40% bone marrow plasmacytosis were excluded. Patients receive lymphodepletion (LD) with fludarabine and cyclophosphamide followed by cilta-cel infusion. The first 6 patients comprise a safety run-in cohort, with the first 3 patients dosed at a lower target dose of 0.5 x 10⁶ CAR-positive T-cells/kg. If there are no dose limiting toxicities (DLTs), the next 3 patients will be dosed at the standard target dose of 0.75 x 10⁶ CAR-positive T-cells/kg. The primary objective of this study is to determine the safety of cilta-cel in HR-SMM. Secondary objectives will assess efficacy, MRD negativity rates and progression-free survival. Correlative studies will assess in vivo proliferation, persistence, and activation of CAR T-cells after infusion as well as characteristics of malignant cells and the tumor microenvironment.

Results: Six patients have been treated in the safety run-in with a median follow up of 6 months (60 days to 1 year). The median age is 55 (range 53-66) with 3 females and 3 males. The isotypes were IgG (4), light chain only (1) and IgD (1). No DLTs were observed in the safety run-in for both 0.5 and 0.75 x 10⁶ CAR-positive T-cells/kg doses. Accrual of additional patients at the dose of 0.75 x 10⁶ CAR-positive T-cells/kg is ongoing.

Grade 3 or greater hematologic toxicities were expected, transient and attributed to LD (neutropenia 100%, anemia 33%, thrombocytopenia 17%). Grade 3 or greater non-hematologic toxicities included AST and ALT increased (17%, during CRS and expected), hypertriglyceridemia (17%), and lymphocytosis (17%). No grade 3 or greater infections have been observed to date.

All patients experienced low grade cytokine release syndrome (CRS) (Grade 1 in 67% and grade 2 in 33%) and no high grade CRS events were observed. Tocilizumab was administered to 4 patients and 2 patients received dexamethasone. There have been no instances of ICANS, Parkinsonism or secondary malignancies to date. One patient experienced grade 1 Bell’s palsy that was self-limiting and resolved within 2 weeks. One patient experienced grade 4 immune related thrombocytopenia secondary to fludarabine, which resolved within 2 weeks after treatment with dexamethasone, IVIG and romiplostim.

CAR T-cells expanded in all patients with peak expansion on days 12-14 after infusion. By flow cytometry, median absolute CAR+T cell count at peak expansion was 3.8 K/uL (range 0.7 – 30 K/ul). CAR T cells were predominately CD4+ with an effector memory phenotype and remained detectable at 3 months in 2 patients. CAR T cell expansion and persistence were similar at both dose levels.

All patients achieved MRD negativity at 10^-6 by day 28 and MRD negativity is sustained in all patients to date without any evidence of progression. The overall response rate is 100%, with complete response rate of 50% and responses deepening over time, consistent with delayed paraprotein clearance in the setting of MRD negativity.

Conclusions: This is the first study of CAR T-cell therapy in a precursor cancer setting, where cilta-cel was used as a primary therapy with no induction therapy for patients with HR-SMM. There have been no DLTs in the safety run-in cohort. CRS was minimal and no ICANS were observed and there were no grade 3 or greater infections. All patients achieved MRD negative (10^-6 ) disease and long-term follow up is required to determine whether these responses will be sustained. The benefit of no induction therapy and potential long-term remissions may be disruptive for future therapeutic algorithms in MM.

Abstract Summary:

• ISB 2001, a trispecific T cell engager targeting BCMA and CD38, demonstrated a favorable safety profile with no dose-limiting toxicities (DLTs) observed up to 600 μg/kg in heavily pre-treated relapsed/refractory multiple myeloma (RRMM) patients.
• The most common adverse event was cytokine release syndrome (CRS), occurring in 71.4% of patients, primarily as Grade 1, with no treatment discontinuations or treatment-related deaths reported.
• The overall response rate (ORR) was 75% among efficacy-evaluable patients, with responses observed at doses as low as 50 μg/kg and a 90% ORR at doses ≥50 μg/kg.
• Pharmacokinetic data indicated a dose-linear increase in serum exposure, with a tentative half-life of 12 days, and transient T-cell activation consistent with the drug’s mechanism of action.
• ISB 2001 showed sustained objective responses, including minimal residual disease (MRD) negativity and stringent complete responses (sCR), supporting its continued dose escalation and further evaluation in Phase 2.

Abstract
Background: Despite advances, MM remains an incurable disease and resistance mechanisms are emerging. ISB 2001 has been designed to overcome tumor escape mechanisms inherent to current MM therapies, such as tumor associated antigen (TAA) downregulation. ISB 2001 is a first in class trispecific T cell engager using Ichnos’ Bispecific Engagement by Antibodies based on the T cell receptor (BEAT^®) heavy chain heterodimerization technology that redirects cytotoxic T cells to BCMA and/or CD38 expressing myeloma cells. Simultaneous targeting of two TAA by ISB 2001 increases avidity binding to tumor cells with low expression of BCMA or CD38 (Carretero-Iglesia at al., AACR 2024, abstract #1238). We report here first-time data from the early dose-escalation portion of an ongoing, multi-center, single-agent Phase 1 study of ISB 2001.

Study design: This study assesses the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of ISB 2001 in RRMM patients(pts). This study is enrolling pts who have received immunomodulatory drugs, proteasome inhibitors, and anti-CD38 therapies either in combination or as a single agent, and are refractory to, or intolerant of, established therapies known to provide clinical benefit in MM. Prior BCMA targeted and/or T-cell directed therapies were allowed.

ISB 2001 is administered weekly by subcutaneous (SC) injection in 28-day cycles, with two step-up doses on cycle 1 day 1 (C1D1) and C1D4 before administering the full target dose on C1D8.

To enable early exposure to the expected efficacious dose, an accelerated dose escalation strategy for the initial 3 cohorts was followed by a conventional 3+3 dose escalation design. The primary outcome measure is the number of dose-limiting toxicities (DLTs) during the first 28 days after the first study treatment. After completion of Part 1 (dose escalation) the study will continue with Part 2 (dose expansion) (FDA Project Optimus) to confirm safety and to select the recommended Phase 2 dose (RP2D).

Results: Based on data extracted on 29-Jul-2024, 14 pts were treated with ISB 2001 in dose escalation: target dose 5 μg/kg (n =1); 15 μg/kg (n =1); 50 μg/kg (n =1); 150 μg/kg (n =4); 300 μg/kg (n =3); 600 μg/kg (n =4)and received at least one cycle of ISB 2001. Median age was 66y; 57.1% male, 92.9% white. Pts had median of 4 prior regimens (range: 2 to 10). All 14 pts were triple-exposed, 9/14 penta-exposed (3/9 penta-refractory). Median follow-up was 2.2 months (range, 1.0 to 6.6). No DLT was observed. AEs of special interest were : injection site reaction Grade (Gr) 1 in 7 pts; lower and upper respiratory tract infection in the same patient (Gr2 and Gr1, respectively) and one Gr3 urinary tract infection; no ICANS were reported; CRS occurred in 71.4% (10 out of 14) of the pts. All were Gr1, except one Gr2. CRS was most common after the first priming dose (64.3% of pts), 14.3% post C1D4, 7.1% post C1D8. Median time to CRS was 2 days with a median duration of 1.5 days (range: 1 to 4). Tocilizumab was used in 3 patients. No patient discontinued the treatment due to a TEAE and no treatment-related death was reported.

During the dose escalation, Overall Response Rate (ORR) was 75% (9 of 12 efficacy-evaluable pts) across all doses, stringent CR (sCR), MRD negative was 8.3%, VGPR 16.7% and PR 50.0%. Objective response was observed with dose level as low as 50μg/kg and ORR in doses ≥50μg/kg was 90%. Median time to response was 36 days (range: 29 to 57) with responses deepening over time. 100% (9/9) of responses were still on treatment at data extract. ISB 2001 was slowly absorbed into the circulation after weekly dosing with T_max generally occurring 7 days post dosing. PK data up to 150 µg/kg indicate general dose linear increase in serum exposures and available data imply a tentative half-life of 12 days . Transient increases in T-cell activation, proliferation and functional markers were observed following ISB 2001 administration, consistent with the T-cell dependent mechanism of action.

Conclusion: ISB 2001, a novel, FIH, BCMAxCD38xCD3 trispecific antibody is well tolerated with low grade CRS and manageable safety profile up to 600 μg/kg. Sustained objective responses were demonstrated from 50μg/kg (MRD neg, sCR) in pts with heavily pre-treated RRMM, with a high ORR of 75% across dose levels. Dose-escalation continues with no DLT observed thus far (NCT05862012).

Abstract Summary:

• MEZI, combined with DEX and either BORT (MeziVd) or CFZ (MeziKd), demonstrated significant clinical activity in patients with relapsed/refractory multiple myeloma (RRMM), with overall response rates (ORR) of 75.0% and 85.2% in the dose-escalation cohorts, and 85.7% in the dose-expansion cohort.
• The most common grade 3/4 treatment-emergent adverse events (TEAEs) were hematologic, including neutropenia and thrombocytopenia, while non-hematologic TEAEs were low or absent, indicating a manageable safety profile.
• MEZI exposure increased dose-linearly, with the 1.0 mg dose showing the greatest pharmacodynamic effects, supporting its use in combination with proteasome inhibitors.
• Median progression-free survival (PFS) was 11.8 and 13.5 months in the dose-escalation cohorts and 17.5 months in the dose-expansion cohort, indicating durable responses.
• The study’s findings support the continued development of MEZI in combination therapies for RRMM, informing ongoing and planned phase 3 trials.

Abstract
Introduction: MEZI is a novel, potent, oral CELMoD™ agent with enhanced tumoricidal and immune-stimulatory effects compared with immunomodulatory drugs (IMiDs^®). Preclinically, MEZI has shown marked synergy with DEX and other antimyeloma therapies, including proteasome inhibitors (PIs). In the phase 1/2 CC-92480-MM-002 trial (NCT03989414), MEZI combined with DEX and BORT (MeziVd) or DEX and CFZ (MeziKd) showed meaningful clinical activity and manageable tolerability in pts with RRMM. Here we report updated results with longer follow-up from the MeziVd and MeziKd dose-escalation cohorts (A and C) and the MeziVd dose-expansion cohort (D).

Methods: Eligible pts had RRMM, 2–4 (Cohorts A and C) or 1–3 (Cohort D) prior regimens including lenalidomide, and documented progressive disease (PD) during or after the last myeloma therapy. Oral MEZI was given at escalating doses of 0.3, 0.6, or 1.0 mg (Cohort A) or at 0.6 or 1.0 mg (Cohort D) on days (D)1–14 of each 21-D cycle with BORT + DEX, or at escalating doses (0.3, 0.6, or 1.0 mg) on D1–21 of each 28-D cycle with CFZ + DEX (Cohort C). Pharmacokinetics samples were collected on D1 and D8 of cycle (C)1 and D8 of C2–8, and also on C1D11 for Cohorts A and D. Biomarker analyses included peripheral blood samples collected on C1D1 to mid-C3 for substrate degradation and immunomodulation by flow cytometry. The primary objectives were to determine the recommended dose and regimen (dose-escalation cohorts) and evaluate safety and efficacy.

Results: As of May 9, 2024, 104 pts were enrolled in Cohorts A, C, and D; 28 pts received MeziVd (Cohort A) and 27 pts received MeziKd (Cohort C) in the dose-escalation cohorts. Median (range) age was 65.5 (46–86) and 68 (41–76) years (y), median time since diagnosis was 4.8 (1.9–17.1) and 5.4 (0.7–15.7) y, median number of prior regimens was 3 (2–4) and 2 (2–4), 24 (85.7%) and 24 (88.9%) pts were refractory to IMiD agents, and 14 (50.0%) and 14 (51.9%) to PIs, respectively. Median follow-up was 13.6 (MeziVd) and 15.2 months (mo) (MeziKd); 3 (10.7%) and 5 (18.5%) pts continue on treatment, with 12.5 and 12 median cycles received, and PD being the main reason for discontinuation (64.3% and 48.1%), respectively.

In the dose-escalation cohorts, the most common grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (35.7%), thrombocytopenia (21.4%), and infections (17.9%) with MeziVd; and neutropenia (44.4%) and infections (33.3%) with MeziKd. Grade 3/4 non-hematologic TEAEs, including rash and diarrhea, were low or absent. MEZI dose reductions due to TEAEs were needed in 7 (25.0%) and 8 (29.6%) pts. The overall response rate (ORR) was 75.0% (21/28 pts) and 85.2% (23/27 pts), with ≥ very good partial responses (VGPR) in 39.3% and 44.4% pts. Median (95% CI) duration of response (DOR) was 10.9 (8.1–18.7) and 11.9 (6.4–NA) mo and median (95% CI) progression-free survival (PFS) was 11.8 (9.0–18.0) and 13.5 (8.4–19.7) mo, respectively.

As of May 9, 2024, 49 pts received MeziVd in the Cohort D dose-expansion cohort. Median age was 64 (43–83) y, median time since diagnosis was 4.2 (0.9–20.5) y, and median number of prior regimens was 1 (1–3). Overall, 31 (63.3%) pts were refractory to IMiD agents, and 8 (16.3%) to PIs. Median follow-up was 18.3 mo; 9 (18.4%) pts continue on treatment, with 15 median cycles received. Discontinuations were mainly due to PD (53.1%).

The most common grade 3/4 TEAEs were neutropenia (63.3%), infections (32.7%), and thrombocytopenia (26.5%); grade 3/4 non-hematologic TEAEs remained low or absent. MEZI dose reductions due to TEAEs were needed in 18 (36.7%) pts. ORR was 85.7% (42/49 pts) with ≥ VGPR in 63.3% of pts; median DOR was 19.4 (9.7–NA) mo, median PFS was 17.5 (9.4–24.0) mo.

MEZI exposure increased in a dose-linear manner over the dose range, and exposures were similar when comparing pts treated with MeziVd and MeziKd. MEZI showed pharmacodynamic activity with BORT or CFZ across all doses tested, with 1.0 mg MEZI inducing the greatest pharmacodynamic effects including substrate degradation and T-cell proliferation, supporting the use of 1.0 mg MEZI in combination with PIs.

Conclusions: With longer follow-up, MeziVd and MeziKd in RRMM confirmed promising efficacy and a manageable safety profile at all dose levels tested, with no cumulative toxicity and low grade 3/4 non-hematologic TEAEs (including rash and diarrhea). These results informed ongoing and planned phase 3 trials. Updated data will be presented at the meeting.

Abstract Summary:

• In the MagnetisMM-20 Phase 1b study, the combination of ELRA, CFZ, and DEX showed promising clinical efficacy in patients with relapsed or refractory multiple myeloma (RRMM), achieving an unconfirmed overall response rate (ORR) of 100% and a confirmed ORR of 83.3% at a median follow-up of 3.24 months.
• No dose-limiting toxicities (DLTs) were observed at either dose level of ELRA, indicating a manageable safety profile. Common adverse events included fatigue, cytokine release syndrome (CRS), and hematological toxicities such as neutropenia and thrombocytopenia.
• The median time to response (TTR) was 1.41 months, and the median duration of response (DOR) was not reached, suggesting durable responses.
• The study continues to enroll patients to further evaluate the safety and efficacy of the ELRA + CFZ + DEX combination in a larger cohort.

Abstract
BACKGROUND

ELRA, a bispecific antibody targeting B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, induced deep and durable responses with a manageable safety profile in the phase 2 registrational MagnetisMM-3 study (NCT04649359) in patients (pts) with RRMM and no prior BCMA-directed therapy (Lesokhin et al, Nat Med 2023). Combining ELRA with CFZ, which has been shown to inhibit myeloma cell proliferation and survival, may enhance activation of immune surveillance of MM cells through different and complementary mechanisms. Here we present results from part 1 of MagnetisMM-20 (NCT05675449), a Phase 1b, open-label, non-randomized study of ELRA + CFZ + DEX.

METHODS

Eligible pts (≥ 18 years) had MM relapsed or refractory to their last anti-MM therapy, 1-3 prior lines of therapy, Eastern Cooperative Oncology Group performance status ≤1, and no prior BCMA-directed therapy. Prior CFZ treatment (tx) was allowed if the pt had ≥PR to most recent CFZ-containing therapy, CFZ was not discontinued due to toxicity, and the pt did not relapse ≤60 days after CFZ discontinuation and had ≥6 month CFZ-free interval before study tx. Pts received a priming dose regimen (cycle 0) consisting of premedication and 2 step-up priming doses of subcutaneous ELRA (12 mg on day 1 and 32 mg on day 4) before the first full dose of ELRA on day 8, either 44 mg (dose level [DL] 1) or 76 mg (DL2) ELRA. ELRA was then given once weekly (QW) and in combination only after the first full dose of ELRA was administered in cycle 0. Pts who receive ≥6 months of QW dosing and achieve ≥ partial response lasting at least 2 months will be transitioned to a once every 2 weeks (Q2W) dosing schedule. Pts received 20 and 70 mg/m² CFZ intravenously on days 1 and 8 of cycle 1, followed by 70 mg/m² on days 1, 8 and 15 of each 4-week cycle, and 40 mg DEX either orally or intravenously QW. Tx will continue until disease progression, unacceptable toxicity, withdrawal of consent or study termination. The primary endpoint is dose limiting toxicities (DLTs) from cycle 0 day 1 through the end of cycle 1 (a total of 42 days). Secondary safety endpoints include adverse events and laboratory abnormalities graded using the NCI CTCAE (version 5.0). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity were graded by ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Secondary efficacy endpoints include best overall response, objective response rate (ORR), complete response rate, time to response (TTR), duration of response (DOR) and progression-free survival (PFS) (all per International Myeloma Working Group criteria), and overall survival (OS).

RESULTS

Of the 12 treated pts in part 1, the median age was 66.0 years (range, 45.0-80.0), 8 (66.7%) were male, none had extramedullary disease, 3 (25.0%) had high-risk cytogenic abnormalities, 4 (33.3%) had ISS stage III, and 8 (66.7%) had <30% baseline bone marrow plasma cells. Eight pts (66.7%) had Revised International Staging System disease stage I or II (unknown for 2 pts [16.7%]). Pts had a median of 2 prior lines of therapy (range, 1-3), and 41.7% had triple-class refractory disease. No pts had a stem cell transplant. At the time of data cutoff (February 22, 2024), 91.7% of pts were ongoing ELRA and CFZ tx, with DEX tx ongoing in 66.7% of pts. Median tx duration was 3.15 months (range, 0.56-13.37).

Among the 10 pts evaluable for DLTs, none were reported at DL1 or DL2. In the safety analysis population (n=12), the most common adverse events (any grade [≥50%], grade 3/4 [≥10%]) were fatigue (83.3%, 8.3%), CRS (75.0%, 0%), neutropenia (58.3%, 33.3%), thrombocytopenia (58.3%, 25.0%), injection site reaction (50.0%, 0%), leukopenia (50.0%, 16.7%), anemia (41.7%, 25.0%), lymphopenia (33.3%, 25.0%), peripheral edema (33.3%, 16.7%), increased blood alkaline phosphatase (25.0%, 16.7%), and pulmonary embolism (16.7%, 16.7%). Infections were reported in 75.0% of the pts, all grade 1/2. No ICANS was reported in any pt.

At a median follow-up of 3.24 months (range, 1.51-13.47), the unconfirmed ORR by investigator was 100%. Ten pts (83.3%) had confirmed ORR by investigator with a median TTR of 1.41 months (95% CI, 0.53-3.35). Median DOR was not reached.

CONCLUSIONS

ELRA + CFZ + DEX has demonstrated clinical efficacy and predictable safety signals. The study continues enrolling and will explore the combination of ELRA + CFZ + DEX in a larger group of pts.

Abstract Summary:

• Inobrodib, combined with pomalidomide and dexamethasone, shows promising efficacy in heavily pre-treated relapsed/refractory multiple myeloma (RRMM) patients, including those refractory to pomalidomide.
• Objective response rates (ORR) were highest (75%) in the highest dose cohort, with rapid and deepening responses over time, even in patients previously treated with anti-BCMA and TCE therapies.
• The treatment regimen is generally tolerable, with Grade 3/4 treatment-emergent adverse events (TEAEs) primarily hematological, consistent with the known safety profiles of the individual agents.
• No significant increase in thrombocytopenia frequency or severity was observed with the triplet therapy, and inobrodib monotherapy did not cause neutropenia.
• The study supports further dose expansion and optimization, with ongoing recruitment and preliminary pharmacodynamic data guiding future pivotal trials.

Abstract
Background

Inobrodib (CCS1477) is a first-in-class potent, selective, and orally bioavailable inhibitor of the conserved bromodomains of p300 and CBP, two closely related histone acetyl transferases with oncogenic roles in hematological malignancies. Inobrodib exhibits potent anti-tumor cell activity in a range of hematological cell lines including multiple myeloma, and demonstrates synergistic activity with pomalidomide.

Aims:

We report an update on safety (primary objective) and efficacy (secondary) data for inobrodib in combination with pomalidomide (pom) and dexamethasone (dex) from relapsed/refractory multiple myeloma (RRMM) patients treated in the Phase I/IIa trial (NCT04068597).

Methods:

Eligible patients (pts) had confirmed RRMM and had exhausted available or suitable standard of care treatment options. Three dose escalation combination cohorts were completed; inobrodib 25mg, or 35mg, bid on a 4 days on/3 days off intermittent schedule with 4mg pom; or inobrodib 25mg bid 4 days on/3 days off with 3mg pom. All regimens were 28-day cycles and included a standard dose of dex, 20-40mg depending on age. Each cohort was further expanded to include up to 10 patients. Adverse events were graded by CTCAE v5.0. Responses were investigator assessed per IMWG. Pharmacodynamic (PD) profiling of paired bone marrow samples and serial PBMC samples, using CyTOF for IRF4, MYC, and other markers is ongoing.

Results:

Dose escalation cohorts have enrolled 48 RRMM pts to date with a median age of 68 yrs (range 41-82). Median prior lines of therapy was 6 (range 2-10), all were triple-class exposed, 39 pts (81%) were triple class refractory, and 16 pts (33%) received prior BCMA therapy. In addition, 31 pts (65%) were pomalidomide-refractory.

Median duration of treatment for 36 evaluable patients to date was 177 days (range 35-601), with a median of 6 cycles (range 1-21). Over 1/3^rd of the patients continue on treatment. Almost 1/3^rd of patients have died in the survival follow-up, mainly due to disease progression, but a number of patients remain in follow-up for overall survival.

At the data cut-off (4^th June 2024), Grade (gr) 3/4 treatment-emergent adverse events (TEAEs) were reported in 35 of 48 (73%) pts. The most frequent gr 3/4 events were hematological (56%); neutropenia (27%: 19% gr 3, 8% gr 4), thrombocytopenia (27%: 21% gr 3, 6% gr 4) and anemia (13%, all gr 3). Frequency of gr 3/4 infections was 29%. This is in line with the anticipated profile of pom/dex only. The main potential for overlapping toxicity is thrombocytopenia however no significant increase in frequency or severity has been seen with the triplet. Inobrodib as monotherapy has not been shown to cause neutropenia. One patient died due to an unrelated cardiac event at the end of cycle 2. Five pts (10%) discontinued due to TEAEs. The pattern of TEAEs considered related to study treatments is consistent with the known safety profile of the individual agents, with the majority of events gr 1/2 and the most common gr 3/4 events being hematological toxicities.

Objective responses were seen across all dose levels tested with best ORR (6/8 evaluable patients, 75%) in the highest dose cohort. In general responses start rapidly after initiation of treatment and deepen with time on treatment.

Among pom-refractory pts, 7 had progressed on a pom-containing regimen as the last prior therapy and 5 of these achieved OR, providing clinical proof of concept on published non-clinical data regarding the exquisite synergy of this combination (Welsh et al. 2024). Responses were also seen in patients exposed to anti-BCMA and/or TCE therapies; further recruitment is ongoing in this population.

In the initial sample of pom-naive pts (12), there is a trend for deeper response with 2 patients achieving CRs (17%) and 2 patients having MRD negativity 10^-5 .

Summary:

The first in class agent inobrodib in combination with pom-dex (all oral combination) shows promising early efficacy in heavily pre-treated, including pom-refractory, RRMM patients. The combination is tolerable, with no overt overlapping toxicity, based on the anticipated safety profile of inobrodib and pom/dex doublet. Preliminary PD data, safety and efficacy will be used to support dose expansion and dose optimisation decisions in the current study, before a pivotal trial is initiated.

Abstract Summary:

• Lisaftoclax, a novel BCL-2 inhibitor, demonstrated promising antitumor activity in patients with relapsed/refractory multiple myeloma (R/R MM) and AL amyloidosis when combined with pomalidomide and dexamethasone (Pd) or daratumumab, lenalidomide, and dexamethasone (DRd).
• In Arm A (Pd combination), the overall response rate (ORR) was 61.3%, with 32.3% achieving very good partial remission (VGPR) or better. In Arm B (DRd combination), all evaluable patients achieved VGPR or better, with a 50% complete remission (CR) rate. In Arm C (Pd for AL amyloidosis), the ORR was 85.7%, with 71.4% achieving VGPR or better.
• The safety profile of lisaftoclax was favorable, with 69.4% of patients experiencing treatment-related adverse events (TRAEs), primarily hematologic, such as neutropenia (20.4%). Serious TRAEs were infrequent, and no significant drug-drug interactions were observed.
• The study supports the potential of lisaftoclax in enhancing treatment outcomes for R/R MM and AL amyloidosis, warranting further investigation.

Abstract
Introduction

MM is characterized by the proliferation of abnormal clonal plasma cells, causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Treatment of MM involves immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies to achieve disease remission. AL amyloidosis comprises disorders of abnormal extracellular deposition of misfolded proteins in various organs with resultant damage, and the key strategy of treatment is to prolong the time to or reverse organ dysfunction. However, many patients will relapse from the standard triplet or quadruplet therapies, necessitating additional treatments with novel mechanisms of action. Lisaftoclax is a novel investigational BCL-2 inhibitor with strong antitumor activity in hematologic malignancies. Here, we report clinical trial data on lisaftoclax combined with novel therapeutic regimens in pts with R/R MM or R/R AL amyloidosis.

Methods

Eligible patients had an ECOG performance status ≤ 2, ≥ 1 prior line of therapy, and adequate organ function. Patients with R/R AL amyloidosis had confirmed symptomatic organ involvement, purpura, and/or carpal tunnel syndrome. Lisaftoclax was administered orally daily at doses assigned in repeated 28-day cycles. Pomalidomide, daratumumab, and lenalidomide were administered per label use. Dexamethasone 40 mg (20 mg, pts > 75 years old) was administered on days 1, 8, 15, and 22 of 28-day cycles. This study evaluated the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Pd; Arm A) or daratumumab, lenalidomide, and dexamethasone (DRd; Arm B) in R/R MM and lisaftoclax combined with Pd in R/R AL amyloidosis (Arm C). Intensive blood samples were collected for pharmacokinetic (PK) analyses.

Results

As of May 29, 2024, 52 pts were enrolled, including 42 with R/R MM and 10 with AL amyloidosis. In Arm A (n = 35), lisaftoclax was administered orally at dose assigned: 400 mg (n = 3), 600 mg (n = 4), 800 mg (n = 15), 1,000 mg (n = 7), and 1,200 mg (n = 6). In Arm B (n = 7), all pts were treated with lisaftoclax 600 mg. In Arm C (n = 10), lisaftoclax was administered at 400 mg (n = 1), 600 mg (n = 4), 800 mg (n = 3), and 1,000 mg (n = 2). The median (range) age of all patients was 69.5 (24-88) years, of whom 63.5% were male and 63.5% were ≥ 65 years of age. The enrolled patients were heavily treated, with a median (range) number of treatment cycles of 4 (1-26), and a median (range) number of prior therapy lines of 3 (1-19). In Arm A, out of 31 evaluable patients, 3 (9.7%) achieved complete remission (CR), 7 (22.6%) reached very good partial remission (VGPR), and 9 (29.0%) achieved partial response (PR). The overall response rate (ORR) was 19 (61.3%), and the ≥ VGPR rate was 10 (32.3%). In Arm B, of 4 evaluable patients, 2 (50%) achieved CR and 2 (50%) ≥ VGPR. In Arm C, of 7 assessed patients, 1 (14.3%) achieved CR, 4 (57.1%) VGPR, 1 (14.3%) PR, and 5 (71.4%) ≥ VGPR, for an ORR of 6 (85.7%); 2 pts had cardiac response.

Among 49 pts in the safety population, 34 (69.4%) reported any-grade lisaftoclax treatment-related AEs (TRAEs; ≥ 5% incidence), including neutropenia (20.4%), thrombocytopenia (6.1%), leukopenia (10.2%), nausea (16.3%), abdominal distension (10.2%), diarrhea (12.2%), and constipation (8.2%). A total of 11 pts experienced grade ≥ 3 TRAEs, including neutropenia (14.3%) and febrile neutropenia (2%), and 3 pts experienced lisaftoclax-related serious AEs (1 each): febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance. In Arm B, 1 pt experienced a dose-limiting toxicity (prolonged QT interval). Pharmacokinetic analyses showed no drug-drug interaction (DDI) in all pts treated with lisaftoclax at all doses in combination with other therapeutic agents used in 3 arms.

Conclusions

Our findings suggest that lisaftoclax improves the depth of response in pts with R/R MM or AL amyloidosis when combined with Pd or DRd. These combination therapies demonstrated a favorable safety profile with no drug-drug interactions, particularly in hematologic side effects. ClinicalTrials.gov registration: NCT04942067; internal study identifier: APG2575MU101.