The 64th American Hematology Annual Conference (ASH) will be held offline and online from December 10 to 13, 2022. This article selects relevant summary of various new immunotherapy such as double antibiotics, CAR-T and ADC announced at the conference. For details, please see below!
ImmunotherapyRelated Summary Selected
01 Bispecific Antibody-Teclistamab
Oral #97
English Title: Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Correlative Analyses from MajesTEC‑1
Key Author: Diana Cortes-Selva
Key information: Baseline correlation analysis of patients undergoing phase 2 recommended doses (RP2D) of clinical trials showed that the immune characteristics at baseline included lower T cell counts; higher expression of T cell expression markers such as PD-1, TIM-3 and CD38 at baseline; more Tregs and CD38+Tregs; and a lower proportion of unsensitized T cells and more NK cells. These data support the clinical combination of Teclistamab with drugs such as Daratumumab or immune checkpoint inhibitors.
Oral #160
English title: Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study
Key Author: Emma Searle
Key information: Initial safety and effectiveness data of patients with multiple myeloma treated with Tec-Dara-Len in the Phase 1b multi cohort study (MajesTEC-2). The median follow-up was 5.78 months and Tec-Dara-Len was found to be safe with good results. The ORR of 13/13 evaluable patients in the 0.72 mg/kg dose group (median follow-up time was 8.61 months), and the ORR of 13/16 evaluable patients in the 1.5 mg/kg dose group (median follow-up time was 4.17 months). The preliminary pharmacokinetic concentration of Tec-Dara-Len is similar to that of Tec monotherapy. This result supports the better control of disease development by early combined Tec treatment regimens.
Poster #1911
English title: Teclistamab Population Pharmacokinetics and Exposure-Response Relationship Support 1.5 Mg/Kg Dose Regimen in Relapsed/Refractory Multiple Myeloma
Key Author: Xin Miao
Key information: The population pharmacokinetics of Teclistamab after intravenous and subcutaneous administration have been fully verified. Exposure-effect analysis of ORR showed that maximum efficacy could be achieved in RP2D, and there was no significant correlation between Teclistamab exposure and adverse events occurring in grade ≥3 blood and infection treatment. These results support that subcutaneous administration of 1.5 mg/kg per week can be used as a recommended dose for the treatment of RRMM.
Poster #4558
English title: MajesTEC-7: A Phase 3, Randomized Study of Teclistamab + Daratumumab + Lenalidomide (Tec-DR) Versus Daratumumab + Lenalidomide + Dexamethasone (DRd) in Patients with Newly Diagnosed Multiple Myeloma Who Are Either Ineligible or Not Intended for Autologous Stem Cell Transplanthamide (Tec-DR) Key Author: Amrita Y. Krishnan
Key information: The MajesTEC-7 trial is a randomized, open, multicenter, phase III clinical trial designed to compare the efficacy of Tec-DR versus DRd in patients with NDMM who are not suitable or not treated with ASCT as initial treatment. The study will open recruitment in the fourth quarter of 2022. The results of the trial may provide a new treatment regimen for improved prognosis (Tec-DR) for patients with NDMM.
Poster #3242
English title: MajesTEC-4 (EMN30): A Phase 3 Trial of Teclistamab + Lenalidomide Versus Lenalidomide Alone As Maintenance Therapy Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma
Key Author: Elena Zamagni
Key information: MajesTEC-4 trial (NCT05243797) is a randomized, open, multicenter, phase III clinical trial aimed at comparing the efficacy of Tec-Len and Len single agent as maintenance treatment in patients with NDMM, who have completed induction therapy and ASCT with or without consolidation therapy. The study, which opened recruitment in May 2022, may reveal a new maintenance regimen that improves response and prolongs survival in patients with NDMM.
02 Bispecific antibody-Talquetamab
Oral #157
English title: Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1
Key Author: Ajai Chari
Key information: MonumenTAL-1 is a phase I/II clinical trial of Talquetamab in the treatment of RRMM patients (NCT03399799/NCT04634552). In the Phase I study, two RP2Ds were selected based on safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data: 0.405 mg/kg per week and 0.8 mg/kg per second week. Among the 143 subjects who received 0.4 mg/kg QW, the ORR was 73% (≥VGPR: 58%; ≥CR: 29%). The most common adverse events are CRS, taste disorders, and anemia. Talquetamab showed good efficacy and safety in RRMM patients who had previously received multiline treatment.
Poster #1937
English title: Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma Treated with Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody: Patient-Reported Outcomes from MonumenTAL-1
Key Author: Cyrille Touzeau
Key information: The study results show that overall HRQoL and body function improved in patients receiving subcutaneous injection of 0.4 mg/kg Talquetamab each week, and significantly reduced pain and fatigue.
Poster #1925
English title: MonumenTAL-3: Phase 3 Trial of Talquetamab + Daratumumab ± Pomalidomide Versus Daratumumab + Pomalidomide + Dexamethasone in Relapsed/Refractory Multiple Myeloma Following ≥1 Prior Line of Therapy
Key Author: Yaël Cohen
Key information: MonumenTAL-3 is a randomized, open, multicenter Phase III clinical trial aimed at comparing the efficacy and safety of Tal-Dara±P and DPd in patients with RRMM with previous LOT ≥1. The study will open recruitment in October 2022.
Poster #3243
English title: MonumenTAL-5: A Phase 3 Study of Talquetamab Versus Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma Who Received ≥4 Prior Lines of Therapy, Including a Proteasome Inhibitor, an Immunomodulatory Drug, and an Anti-CD38 Monoclonal Antibody
Key Author: Shaji K Kumar
Key Information: MonumenTAL-5 is a multicenter, randomized, open-label, active-controlled Phase III clinical trial aimed at comparing the efficacy and safety of Talquetamab monotherapy and Belantamab Mafodotin monotherapy in patients with RRMM with previous LOT ≥4. The study will open recruitment in October 2022. The results of the study will help to gain an in-depth understanding of the efficacy and safety of Talquetamab in patients with severe RRMM compared with Belantamab.
03 Other bispecific antibodies
Poster #1921
English title: Elranatamab in Combination with Daratumumab for Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 3 Magnetismmm-5 Study Safety Lead-in Cohorthamumab 5Key Author: Sebastian Grosicki
Key Information: MagnetisMM-5 (NCT05020236) is an open, multicenter, randomized phase III study aimed at evaluating the efficacy and safety of subcutaneous injection of Elranatamab monotherapy or combined with Daratumumab in patients with RRMM. Results from previous safety trials showed that SC Elranatamab+SC Daratumumab showed good early response and tolerated safety in RRMM patients. In part 2 of MagnetisMM-5, subjects will be randomly treated with SC Elranatamab monotherapy, SC Elranatamab+SC Daratumumab or DPd at a ratio of 1:1:1.
Oral #159
English title: Efficacy and Safety of Elranatamab in Patients with Relapsed/Refractory Multiple Myeloma Naïve to B-Cell Maturation Antigen (BCMA)-Directed Therapies: Results from Cohort a of the Magnetismmm-3 Study
Key Author: Nizar Jacques Bahlis
Key information: 76mg subcutaneous injection per week Elranatamab is effective in patients with triple or five-fold drug-refractory MM and has not received BCMA targeted therapy, and is safe and controllable.
Oral #162
English title: Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study
Key Author: Sandy W. Wong
Key information: Intravenous ALNUC has good efficacy in treating RRMM patients who have received multiline treatment. Subcutaneous injection improves safety compared with intravenous injection, CRS is limited to grade 1-2 adverse reaction events, and subcutaneous injection of ALNUC exhibits dose-dependent anti-tumor activity with a high proportion of MRD response.
04 CAR-T
Poster #3357
English title: Phase 2, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-BCMA CAR-T Cell Therapy, in Chinese Patients with Relapsed/Refractory Multiple Myeloma (CARTIFAN-1): 26-Month Media Follow-up
Key Author: Jian-Qing Mi
Key Information: CARTIFAN-1 is an ongoing phase II open study, with a total of 8 hospitals participating in the study. Follow-up results for up to 26.4 months showed that the ORR remained at 85.4%, and the depth of remission increased, with the sCR reaching 79.2%. The results of the study show that cilta-cel brings deep relief and survival benefits to relapsed/refractory patients who have received previous multiline treatment.
Poster #2023
English title: DVRd Followed By Ciltacabtagene Autoleucel Versus DVRd Followed By ASCT in Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible: A Randomized Phase 3 Study (EMagine/CARTITUDE-6)
Key Author: Mario Boccadoro
Key information: The EMagine/CARTITUDE-6 study is a randomized, open-label, global, multicenter, phase III clinical trial aimed at comparing the efficacy of Cilta-cel and lenalidomide and DVRd after DVRd and lenalidomide in patients with TE NDMM. The study began recruitment in September 2022.
Poster #3354
English title: Ciltacabtagene Autoleucel (Cilta-cel), a BCMA-Directed CAR-T Cell Therapy, in Patients with Multiple Myeloma (MM) and Early Relapse after Initial Therapy: CARTITUDE-2 Cohort B 18-Month Follow-up
Key Author: Niels WCJ Van De Donk
Key information: functionally high risk Among the high-risk patients, all included patients relapsed within 1 year after receiving standard treatment. After receiving Cilta-cel treatment, the 1-year PFS rate was 90%, the ORR was 100%, and the ≥CR ratio was 90%. The results show that this treatment regimen may significantly improve the adverse prognosis of this high-risk population.
Poster #2028
English title: Efficacy and Safety of Cilta-Cel in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy
Key Author: Adam D Cohen
Key information: In patients with severe treatment and BCMA cell therapy, receiving Cilta-cel can achieve better efficacy, but its depth of remission and duration of response are lower than those without BCMA treatment. This result suggests the sequence of treatment and the effect of BCMA target elution period on the therapeutic efficacy of this therapy.
Oral #366
English title: Phase I Open-Label Single-Arm Study of BCMA/CD19 Dual-Targeting FasTCAR-T Cells (GC012F) As First-Line Therapy for Transplant-Eligible Newly Diagnosed High-Risk Multiple Myeloma
Key Author: Juan Du
Key information: BCMA/CD19 dual-target FasTCAR-T therapy in phase 1 clinical study of high-risk NDMM. The research results show that the therapy has good safety, up to 100% effectiveness, and a 100% MRD negative rate. We look forward to bringing more relevant data on TE NDMM treatment in the future.
Oral #766
English title: Idecabtagene Vicleucel (Ide-cel) Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Have Received a Prior BCMA-Targeted Therapy: Real World, Multi-Institutional Experience
Key Author: Christopher J. Ferreri
Key information: The results of a large multi-center retrospective study showed that patients who had previously exposed BCMA treatment received Ide-cel PFS, ORR, and ≥CR were relatively worse, and patients who received Ide-cel within six months of previous BCMA target treatment were less effective. Exploring the timing of treatment with Ide-cel after BCMA treatment requires more clinical evidence.
Oral #364
English title: Clinical Activity of BMS-986393 (CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients with Relapsed and/or Refractory (R/R) Multiple Myeloma (MM): First Results from a Phase 1, Multicenter, Open-Label Study
Key Author: Susan Bal
Key Information: A phase I study result of a multi-center, first-time application in humans and dose exploration shows that the GPRC5D-targeted CAR-T product BMS-986393 has good safety, and most of the neurotoxicity and CRS are low-level, with uncommon neurotoxicity and persistent events; 3-month CR rate and MRD negative rate have good results. In the research design of Part B, there will be more dose-related directions to be explored.
Oral #250
English title: Clinical Outcomes and Salvage Therapies in Patients with Relapsed/Refractory Multiple Myeloma Following Progression on BCMA-Targeted CAR-T Therapy
Key Author: Kevin R Reyes
Key Information: Although BCMA CAR-T treatment can bring higher ORR, long-term PFS results are still not ideal. Patients who relapse after BCMA CAR-T treatment often predict poor prognosis. Immune drugs targeted by BCMA, including BCMA CAR-T or monoclonal antibodies, may be effective treatment methods for this type of patients. Previous treatment-resistant regimens may still be effective for this group of patients, but the duration of continuous remission is limited; this group of people urgently need new treatment methods to improve prognosis.
Poster #2236
English title: Safety and Efficacy of BCMA-Targeted CAR-T Therapy in Geriatric Patients with Multiple Myeloma
Key Author: Kevin R Reyes
Key information: 77 patients were included in this study, and the retrospective analysis showed that CAR-T therapy did not significantly increase toxicity in patients aged ≥70 years; the OS data of elderly patients was significantly better than that of young patients, and this result may be due to sample size limitations and correction at baseline. It has certain research limitations; in short, the research results show that it is safe and effective for elderly patients to receive CART treatment.
Poster #3315
English title: Immune Recovery Post BCMA CAR-T: Implications for Infection Prophylaxis and Vaccinations
Key Author: Shambavi Richard
Key information: After receiving CAR-T treatment for two years, even if these patients are in a complete remission stage, more than one-third of the patients' immune-related indicators IgM, CD3 and B cell have not returned to normal levels; more than half of the patients' IgA indicators have not returned to normal levels; the results of this article show that the degree of recovery of immune indicators in these patients is poor, which also explains the reasons why the vaccine is poor and the risk of infection is high; based on the results of the article, it is also recommended that patients with immunosuppressive status use drug prevention in advance to reduce the risk of infection.
Poster #3222
English title: Impact of High-Risk Disease on Outcome after CAR-T Cell Therapy for Multiple Myeloma: A Meta-Analysis of 759 Patients
Key Author: Nico Gagelmann
Key information: For RRMM patients treated with CAR-T, high cytogenetic risk is significantly correlated with poor prognosis. Judging from the results of this study, extramedullary factors show a significant correlation between the risk of recurrence and poor survival prognosis.
05 Other immunotherapy
Oral #565
English title: Final Results from the First-in-Human Phase 1/2 Study of Modakafusp Alfa, an Immune-Targeting Attenuated Cytokine, in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Key Author: Dan T. Vogl
Key Information: Modakafusp Alfa is a potential "first-in-class" immune-targeting attenuated cytokine that fuses interferon alpha2b that stimulates the immune response at the Fc end of a monoclonal antibody targeting CD38, aiming to deliver the attenuated interferon alpha2b fragment to cells expressing CD38. The results of this study show that the dose of 1.5 mg/kg Q4W has good safety and anti-tumor activity, and is independent of the expression of CD38 in peripheral blood immune cells.
Poster #4549
English title: Belantamab Mafodotin (Belamaf) for Relapsed/Refractory Multiple Myeloma (RRMM): A Real-World Observational Study
Key Author: Malin Hultcrantz
Key information: A real-world study included 137 RRMM patients using Belamaf, which were older and had fewer previous treatment lines compared with the study baseline of DREAMM-2; the overall population ORR was comparable to DREAMM-2 (30.2% vs 31%), the highest proportion of adverse events is corneal lesions, and adverse reactions need to be paid attention to.
Poster #4562
English title: sea-bcma mono- and combination therapy in patients with relaxed/refractory multiple myeloma: updated results of a phase 1 study (sgnbcma-001)
Key author: James E
Key information: SEA-BCMA is a humanized, non-glycosylated IgG1 monoclonal antibody targeting BCMA. The updated research results show that the monoclonal antibody has better safety and the combination regimen with dexamethasone may improve clinical efficacy. Subsequently, Part C2 and Part D included the SEA-BCMA combined with pomalidomide and dexamethasone regimen in patients who received third-line treatment, and looked forward to the announcement of subsequent results.
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Typesetting: Moly
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