Preview of the Black Swan Research Initiative’s First US Cure Trial
This week, Dr. Shaji Kumar shares the details of the upcoming US ASCENT “Cure Trial” in a video interview on IMF-TV. ASCENT stands for Aggressive Smoldering Cure Evaluating Novel Rx Transplant. This long-anticipated clinical trial, expected to launch in late Fall 2016, is based on key tenets of the IMF’s Black Swan Research Initiative® (BSRI)®:
- Start treatment early. The trial is for patients with high-risk smoldering multiple myeloma (HR-SMM). The early start ensures that treatment will be more effective by avoiding potentially dangerous mutations that emerge during the transition from HR-SMM to active myeloma. (I’ve explained this more fully in the recent IMF “Living Well” teleconference.)
- Use the best-combination approach feasibly. The protocol treatment for the ASCENT trial is a four-drug combination of Kyprolis (K)/ Revlimid (R)/ dexamethasone (d)/ daratumumab (dara or Darzalex) – KRd-dara. This combination brings together the three most active myeloma novel therapies plus dexamethasone. It is expected that more than 90% of patients will achieve minimal residual disease (MRD)-negative status as a result. Eligible patients will also proceed with an autologous stem cell transplant (ASCT). Then, all patients will receive a reduced dose of Kyprolis and Revlimid plus dara for one year of maintenance. At this point, a 100% level of MRD negativity is highly likely.
- Sustained MRD negativity. The new 2016 MRD response criteria from the International Myeloma Working Group (IMWG), which is scheduled for publication next week in The Lancet Oncology, includes the very important category of “sustained MRD negativity.” It is with the use of this endpoint that BSRI investigators have structured a framework to define a potential cure. MRD status is tracked at 1, 3, and 5 years. If MRD negativity is retained at 5 years, very long survival and potential cure are anticipated. Conservatively, it is hoped that at least 50% of patients will fall into this category.
The ASCENT trial is an exploratory study to evaluate both the safety and effectiveness of this approach. It is extremely important that all efforts such as this are conducted within the framework of a clinical trial.
The recent results of the POLLUX study give significant grounds for optimism about the benefits of the ASCENT trial. Using only daratumumab plus Rd in the relapse setting, 30% of patients achieved an MRD negative status. Thus, adding dara to KRd—known to be very effective in HR-SMM—should give especially good results.
So, time will tell! We are thrilled that this study is finally getting started soon and will keep everyone posted about the progress.
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*Updated July 23, 2016, to reflect an adjustment to the ASCENT trial: the maintenance portion of the trial has been amended to include Kyprolis and Revlimid plus Darzalex (daratumumab) given every other month for one year. Thanks to the eagle-eyed Dana Holmes for calling our attention to the discrepancy.