Myeloma Research Updates Presented at the 2018 American Society of Hematology (ASH) Annual Meeting
More than 25,000 hematology professionals attended this year’s ASH annual meeting that took place December 1-4 in San Diego. From the 5,000+ scientific abstracts presented, you will find below some of the latest highlights in myeloma research.
MAIA Trial: Daratumumab (Darzalex®), Lenalidomide (Revlimid®) and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Myeloma Ineligible for Transplant
MAIA Study Design
Facon T, et al. ASH 2018. Abstract LBA-2.
In Canada, Rd is the standard of care treatment for newly diagnosed myeloma patients who are ineligible for high-dose therapy and autologous stem cell transplant. Results from the phase III MAIA study demonstrated that adding daratumumab to Rd (D-Rd) significantly reduces the risk of disease progression or death by 44% in this patient population. The D-Rd arm of the study had an overall response rate of 93% compared to 81% in the Rd arm. With regards to progression-free survival (PFS), the median was not reached in the D-Rd arm and it was equivalent to 31.9 months in the Rd arm. Treatment with D-Rd was well tolerated, and its safety profile is consistent with what has been reported in other trials using the same combination.
Bispecific T-cell Engager (BiTE®): Phase I Dose Escalation Study with AMG 420 in Relapsed/Refractory Myeloma Patients
AMG 420 Study Design
Topp MS, et al. ASH 2018. Abstract 1010.
AMG 420 is a BiTE® antibody construct that targets B-cell maturation antigen (BCMA), a protein that is found on the surface of myeloma cells. The first-in-human study enrolled 42 patients with relapsed/refractory myeloma that had progressed after 2 or more prior treatments. Intravenous doses ranging from 0.2 to 800 µg/day were tested and 400 µg/day was found to be the maximum tolerated dose that will be used for further evaluation. Of the 10 patients who received a dose of 400 µg/day, 7 people responded to the treatment and 4 people achieved a minimal residual disease (MRD) negative stringent complete response (sCR). The serious adverse events experienced included cytokine release syndrome, infections, peripheral polyneuropathy and edema. Phase 1b of the study will further evaluate the treatment’s safety and efficiency.
GRIFFIN Trial: Daratumumab (Darzalex®), Bortezomib (Velcade®), Lenalidomide (Revlimid®) and Dexamethasone (D-VRd) Versus Bortezomib, Lenalidomide and Dexamethasone (VRd) in Patients with Newly Diagnosed Myeloma Eligible for High‐dose Therapy and Autologous Stem Cell Transplantation
GRIFFIN Study Design
Voorhees PM, et al. ASH 2018. Abstract 151.
This phase II trial evaluated the safety and efficiencycy of adding daratumumab to VRd (D-VRd) for induction and consolidation therapies, before and after high‐dose therapy and autologous stem cell transplant, respectively. D-VRd was reported to have an overall safety profile consistent with daratumumab and VRd alone and the toxicities observed were manageable. The addition of daratumumab to the regimen did not affect stem cell collection and transplant. Furthermore, the depth of response improved following consolidation therapy, deepened over time and all patients achieved a very good partial response (VGPR).
Chimeric Antigen Receptor (CAR) T-cell Therapy Research is Ongoing in Myeloma
The type of CAR T-cell therapy most commonly being evaluated for the treatment of myeloma targets B-cell maturation antigen (BCMA), a protein that is found on the surface of myeloma cells. Promising results from various BCMA CAR T-cell therapies were presented and each one demonstrated differences in both their efficacy and safety profiles. More studies are needed to properly evaluate the short and long-term risks and benefits of BCMA CAR T-cell therapies.
FORTE Trial: Carfilzomib (Kyprolis®), Lenalidomide (Revlimid®) and Dexamethasone (KRd) Induction Followed by Autologous Stem Cell Transplantation (ASCT) and KRd Consolidation (KRd-ASCT-KRd arm) Versus KRd for 12 Cycles (KRd12 arm) Versus Carfilzomib, Cyclophosphamide, Dexamethasone (KCd) Induction Followed by ASCT and KCd Consolidation (KRC-ASCT-KCd arm) in Newly Diagnosed Myeloma
FORTE Study Design
Gay F, et al. ASH 2018. Abstract 121.
The FORTE trial examined the safety and efficiency of the KCd-ASCT-KCd arm versus the KRd-ASCT-KRd and KRd12 arms. Both KRd-containing treatment arms (KRd-ASCT-KRd and KRd12) demonstrated similar rates of response and minimal residual disease negativity – and both were significantly superior to those observed in the KCd-ASCT-KCd arm. Progression-free survival and overall survival will be evaluated as the trial progresses. The treatments were all well tolerated.
STORM Trial: Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory Myeloma

Selinexor is a novel drug with a unique mechanism of action that is thought to bind with and inhibit the nuclear export protein XPO1 of myeloma cells, leading to their death. Part 2 of the STORM study recruited an additional 122 patients who were refractory to at least 5 prior treatments including: bortezomib (Velcade®), carfilzomib (Kyprolis®), lenalidomide (Revlimid®), pomalidomide (Pomalyst®) and daratumumab (Darzalex®). In this study, selinexor in combination with low-dose dexamethasone. They demonstrated an overall response rate of 26.2%, a median progression-free survival of 3.7 months and a median overall survival (OS) of 8.6 months. In this heavily pre-treated patient population, those who progressed on the treatment had a median OS of 1.7 months.
Click on the links below to know more about the following trials: