Myeloma immune therapy emerges as a key theme at ASCO 2015
The 2015 annual meeting of the American Society of Clinical Oncology (ASCO) is almost upon us. It is being held in Chicago from May 29th to June 2nd. This year, approximately 100 abstracts will focus on myeloma. Thus, although many fewer than at the annual meetings of the American Society of Hematology (ASH), several abstracts of importance to the myeloma community will be presented in Chicago.
Immune therapy in myeloma will likely dominate the news from ASCO, both in general and specifically results with elotuzumab, daratumumab and CAR-T cells (anti-CD19). Results from the Phase III ELOQUENT 2 trial (abstract #8508) with elotuzumab (SLAM-F7 monoclonal antibody) will be presented by Dr. Sagar Lonial from Emory University. In this study of 646 patients, the PFS (progression free survival; remission duration) was increased by 4.9 months (19.4 months versus 14.9 months) in patients who had received 1-3 prior therapies treated with elotuzumab combined with Revlimid/dexamethasone versus Revlimid/dexamethasone alone. This is statistically significant and, as Dr. Lonial put it, “It was particularly striking that the difference between elotuzumab and control groups seems to get bigger over time, which really speaks to the power of this immune-based approach.”
Other investigators, myself included, were expecting longer overall benefit with elotuzumab based upon the somewhat longer remissions seen in the prior Phase II study. The key point, however, is that this is a new class of agent recruiting the activity of natural killer (NK) cells to attack myeloma, which is showing significant benefit. This is a very important addition to the myeloma arsenal. It is widely predicted that these data will be sufficient to lead to favorable review by the US Food and Drug Administration (FDA)—especially since elotuzumab is such a well-tolerated agent, as also shown in a separate study (Jakubowiak et al.) combining elotuzumab with Velcade and dexamethasone, in which the combined synergy is less active.
Perhaps even more highly anticipated is Dr. Lonial’s second abstract (#LBA8512) detailing the results of daratumumab as a single agent in patients with relapsed and refractory myeloma. The direct benefit with this anti-CD 38 monoclonal antibody is expected to be at a level which will qualify daratumumab as fulfilling the FDA criteria for “unmet need” in this advanced disease setting. The final results are embargoed until the last day of the ASCO meeting, and are eagerly awaited.
Another important trial will be presented by Dr. Meletios Dimopoulos (University of Athens, Greece). This is the Phase III ENDEAVOR trial (abstract #8509), in which Kyprolis plus dexamethasone is compared with Velcade plus dexamethasone in the relapse setting. There is a remarkable doubling of PFS (18.7 versus 9.4 months) with Kyprolis versus Velcade in a pattern very similar to benefit seen in the ASPIRE trial, in which Kyprolis was added to Revlimid/dexamethasone. This reinforces the substantial benefit achieved with Kyprolis as a second or next generation proteasome inhibitor.
Additional promising new data will be presented by Dr. Edward Stadtmauer (University of Pennsylvania). He will summarize the results in three patients treated with chimeric antigen receptor (CAR) – T cells directed against the CD19 antigen on myeloma cells. Two patients have achieved MRD-negative complete response (CR), which is durable thus far. The third patient progressed at 43 days. So a small study, but a potentially powerful approach. Definitely an area to watch, although it is important to be aware that only 4-5% of patients have CD19 positive myeloma (usually CD19 is negative). It is hoped there will be more broadly applicable CAR-T therapies developed.
So these are likely to be the headlines coming out of ASCO 2015. Each new study helps guide myeloma therapy and makes new agents potentially available. Look for lots of FDA action in the next 6-9 months! As always, stay tuned for all the next developments.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.