ASH 2017 – Day Three

Afternoon


2:45 PM-4:15 PM
Session 653. Myeloma: Therapy, excluding Transplantation I

Dr. James Kochenderfer from the NIH presented the latest data on the anti-B-cell maturation antigen (BCMA) CAR-T cell therapy bb2121 (ABSTRACT 740). In his Phase 1 study of bb2121 in 21 patients with relapsed/refractory MM (many who had previously received 3 to 14 different regimens), Dr. Kochenderfer and colleagues showed:

  • Of all patients treated, over 90% had a response ; of those patients assessable for minimal residual disease (MRD) testing, 90% were negative
  • 1 case of serious neurotoxicity observed and cytokine release syndrome (CRS) was reported in 71% of patients

To achieve MRD negativity in patients with such highly refractory disease is truly unprecedented. That said, the number of patients treated is still very low and the fact that 71% had CRS, which is potentially life-threatening, underscores the severity of the potential toxicities associated with CAR T-cell therapy. Nevertheless, it remains a truly promising treatment and the MMRF is committed to supporting the continued development of CAR T-cell approaches, as well as the identification of patients most likely to benefit from this approach.

Another type of anti-BCMA CAR-T cell therapy was developed by clinicians at the Memorial Sloan Kettering Cancer Center. This particular CAR-T cell therapy was engineered to be highly specific to the BCMA molecule on the surface of MM cells and to elicit desirable T cell activity. Dr. Eric Smith and his colleagues shared their clinical experience using their CAR-T cell therapy in a pilot trial in 6 patients with relapsed/refractory MM patients (ABSTRACT 742). We learned from Dr. Smith that many patients experienced cytokine release syndrome, but no neurotoxicities and that ~75% of patients (who could be evaluated for response) responded to this new CAR-T cell construct. This is another very early study with promising results, so we will remain cautiously optimistic!

The newest drug class to generate excitement this year is the antibody-drug conjugates (ADC) and Dr. Suzanne Trudel from Princess Margaret Cancer Center in Toronto presented her group’s phase 2 experience with the anti-BCMA ADC GSK2857916 (ABSTRACT 741). The anti-BCMA ADC is an antibody that on one end can target BCMA on the surface of MM cells and on the other end is linked to a toxin that once the ADC binds, can directly kill the MM cell. Thirty-five patients with relapsed/refractory MM (many who had previously received more than 5 different regimens) were treated with GSK2857916 via an intravenous infusion.

Results from the trial revealed that 60% of patients had a response and the most commonly occurring side effect were corneal events (such as blurred vision, dry eye) and low platelet counts.


4:30 PM-6:00 PM
Session 653. Myeloma: Therapy, excluding Transplantation: Studies in Relapsed and Refractory Multiple Myeloma

Monday ended with a session on the latest clinical data on the treatment of patients with relapsed and refractory MM. Such studies included a trial of a subcutaneous formulation of Darzalex (daratumumab)(Abstract 838), gene profiles that may predict response to Kyprolis (carfilzomib) treatment (Abstract 839), and the combination of Revlimid (lenalidomide) and Empliciti (elotuzumab) for use as maintenance therapy following autologous stem cell transplantation (ASCT; Abstract 840).

The use of Darzalex as a subcutaneous injection—rather than the usual intravenous infusion was investigated by Dr. Ajai Chari from Mount Sinai School of Medicine (ABSTRACT 838). Dr. Chari presented his phase 1 study to see if a subcutaneous injection could lessen the frequency of infusion related reactions. In this study, Darzalex was combined with another drug called recombinant human hyaluronidase enzyme (rHuPH20) and the combination was administered in two different ways to relapsed/refractory MM patients: one in which the drugs were mixed and delivered together and given over 20-30 minutes and one in which the drugs were co-formulated together and given in 3 to 5 minutes. Dr. Chari’s results showed us that:

  • Almost all patients discontinued treatment when the drugs were mixed and delivered together; however all patients who received the co-formulated drugs stayed on treatment.
  • Both drug formulations had similar response rates with ~40% of patients responding to the treatments
  • Lower than expected rates of infusion related reactions occurred in all groups, but especially in the group that received the co-formulated drugs

Robert Pelham, PhD from Amgen and his US and EU colleagues involved in the ENDEAVOR trial of Kyprolis + dexamethasone (Kd) versus Velcade + dexamethasone (Vd) used RNA sequencing data from patients on the trial to identify genes that could be used to identify which relapsed/refractory MM patients would benefit from Kd or Vd therapy (ABSTRACT 839). The investigators identified a set of 13 genes whose expression could be used to categorize patients that would derive greatest clinical benefit from Kd. This set of genes will be further validated in other independent studies.

Investigators from MD Anderson Cancer Center led by Dr. Sheeba Thomas presented their phase 2 trial results of safety and efficacy of adding Empliciti to Revlimid as a maintenance therapy strategy following ASCT (ABSTRACT 840). Preliminary results from the study showed:

  • Empliciti+Revlimid is well-tolerated as maintenance
  • Thirty-six percent of patients improved their initial disease response while on therapy (with some converting to complete responses and some with MRD negativity)

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