ASH 2018 Multiple myeloma – congress summary
The American Society of Haematology (ASH) conference is a multi-disciplinary platform for haematology education and scientific exchange, and a great opportunity for academics and clinicians to make their scientific discoveries internationally heard. This year proved again to be an exciting and thought-provoking meeting, with a broad agenda including oral and poster sessions, workshops, and an extensive educational program.
MYELOMA ABSTRACTS OF INTEREST
ASH provides an excellent international forum for the presentation of the latest pioneering and potentially practice-changing research. Shown below is a selection of this year’s top abstracts in multiple myeloma (MM), some of which could revolutionise the MM patient pathway in the future.
CAR-T CELLS MAY BE A HIGHLY EFFECTIVE THERAPY FOR RRMM1
Chimeric antigen receptor T-cell (CAR-T) therapy was one of the hot topics at ASH 2018, with a large number of abstracts and presentations indicating that this could be a potentially game-changing treatment in many blood cancers, including MM. Zhao and colleagues presented data that showed LCAR-B38M, a bispecific CAR-T cell therapy directed against B-cell maturation antigen (BCMA), displayed a manageable safety profile and a promising overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (RRMM).
TANDEM ASCT, AND COMBINED CAR-T-19 AND CAR-T-BCMA CELLS COULD BE AN OPTION FOR CONSOLIDATION TREATMENT2
Survival remains poor in high-risk patients with MM, such as those with Revised International Staging System stage III disease, constituting a significant unmet need in MM. Shi et al. demonstrated the potential role of tandem autologous transplant (ASCT) and combined infusion of CD19 and B-cell maturation antigen (BCMA)-specific CAR-T cells as a choice of consolidation therapy for high-risk MM patients. Minimal residual disease-negativity was achieved in 66.7% of the 9 patients who have completed CAR-T cells infusion with mild and reversible toxicities.
MYELOMA XI SHOWS PROMISING RESPONSES IN TRANSPLANT-ELIGIBLE NDMM PATIENTS3
The UK Myeloma XI trial led by Professor Graham compared immunomodulatory drug (IMiD) triplet combinations to a carfilzomib plus IMiD triplet combination as a therapy in transplant eligible, newly diagnosed multiple myeloma (NDMM) patients. The results presented unequivocally showed that an intensified induction of a quadruplet regimen leads to deep responses both pre- and post-transplant with a manageable toxicity profile.
MYELOMA XI SHOWS THAT A PFS <12 MONTHS FOLLOWING ASCT IS A HALLMARK OF HIGH-RISK DISEASE4
The duration of progression-free survival (PFS) is variable between patients with MM. This landmark analysis of the Myeloma XI trial revealed that nearly 75% of patients relapsing within 12 months of treatment had died 3 years after entry to Myeloma XI. Continuous lenalidomide therapy did not prevent early progression in some patients. This highlights the urgent unmet need in this poorly understood group.
MUK Five DEMONSTRATES THAT KCD IMPROVES ≥VGPR RATE VS VCD IN PATIENTS WITH ADVERSE GENETIC RISK5
This long-term follow-up of the Phase II Muk five trial conducted by Professor Kwee Yong and colleagues examined the efficacy and safety of carfilzomib (K) and bortezomib (V) in triplet combination with cyclophosphamide and dexamethasone (Cd) for patients at first relapse, or refractory to no more than one prior line of therapy, and investigated the benefit of K maintenance following fixed duration KCd. In patients with adverse genetic risk, it was shown that KCd is non-inferior to VCd, and achieves a higher very good partial response (VGPR) rate. A greater benefit was also shown in ORR in patients with early relapse and pre-transplantation.
THE MAIA STUDY SHOWS THAT THE ADDITION OF DARATUMUMAB TO RD IN PATIENTS WITH TRANSPLANT-INELIGIBLE NDMM SIGNIFICANTLY REDUCED THE RISK OF PROGRESSION OR DEATH6
The MAIA study evaluated the efficacy and tolerability of daratumumab, lenalidomide and dexamethasone (DRd) vs lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). This interim analysis reported a 45% reduction in the risk of progression or death in patients treated with DRd compared to those treated with Rd. Adding daratumumab to Rd also resulted in deeper responses. No new safety signals were observed.
PROMISING RESULTS WITH NEW IMMUNE MODALITY AMG 4207
AMG 420, an anti-BCMA bispecific T-Cell engager (BiTE®), binds BCMA on tumour cells and plasma cells, and CD3 on T cells. This causes T-cell mediated lysis of BCMA+ MM and plasma cells. This first-in-human study by Topp and colleagues found that treating RRMM patients (n=35) with AMG 420 showed promising activity, with some patients achieving minimal residual disease-negative complete responses without major toxicities.
1. Zhao W et al. Abstract 955. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018. Available at: https://ash.confex.com/ash/2018/webprogram/Paper110548.html. Accessed January 2019.
2. Shi X et al. Abstract 1009. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper117964.html. Accessed January 2019.
3. Jackson G et al. Abstract 302. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper114956.html. Accessed January 2019.
4. Bygrave C et al. Abstract 122. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper111117.html. Accessed January 2019.
5. Yong K et al. Abstract 306. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper116624.html. Accessed January 2019.
6. Facon T et al. Abstract LBA-2. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper120737.html. Accessed January 2019.
7. Topp M et al. Abstract 1010. Presented at the 60th American Society of Hematology Annual Meeting & Exposition 2018.Available at: https://ash.confex.com/ash/2018/webprogram/Paper109769.html. Accessed January 2019.