The Multiple Myeloma Hub are delighted to have attended the 2017 ASCO Annual Meeting held in Chicago, Illinois from 2nd to 6th June. Multiple Myeloma (MM) was covered extensively in numerous oral and poster sessions. One of the MM treatments that featured prominently was daratumumab - a humanized anti-CD38 monoclonal antibody approved for the treatment of MM in the relapsed and refractory setting. Several clinical trials are ongoing, to test the efficacy of daratumumab with different drug combinations.
Two poster presentations provided updated data from ongoing phase 3 clinical trials: the POLLUX trial to assess the efficacy of adding daratumumab to lenalidomide and dexamethasone, and the CASTOR trial in which daratumumab is combined with bortezomib and dexamethasone (both previously described on the MM Hub).
Updated data was provided by Nizar J. Bahlis from the Tom Baker Cancer Centre, Calgary, Canada, from the POLLUX clinical trial, in which heavily pre-treated patients (receiving from 1 -11 prior treatment regimens) were given either lenalidomide and dexamethasone (Rd) or daratumumab, lenalidomide and dexamethasone (DRd). DRd significantly prolonged PFS - median: not reached as compared with 17.5 months in a previous assessment (HR = 0.37; 95% CI, 0.28-0.50; P< 0.0001). DRd also led to a significantly improved overall response rate (ORR = 93% vs. 76%, P< 0.0001) and led to higher rates of deep responses: ≥very good partial response [VGPR] = 78% vs 45%; ≥CR = 46% vs 20% (P< 0.0001). MRD negativity was > 3-fold higher for DRd compared with Rd across all sensitivity thresholds: 25% vs. 6% at 10–5 and MRD-negativity correlated with a longer PFS.
Updated data from the CASTOR clinical trial was provided by Suzanne Lentzsch, from the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA, in which heavily pre-treated patients (receiving from 1 -10 prior treatment regimens) were given bortezomib and dexamethasone (Vd), or daratumumab, bortezomib and dexamethasone (DVd). The addition of daratumumab led to a significantly prolonged PFS compared to treatment without: median not reached vs. 7.1 months; HR = 0.33; 95% CI, 0.26-0.43 (P< 0.0001). Prior treatment regimens did not affect the overall PFS benefit, although a greater benefit was observed in the least heavily pre-treated patients. The overall response rate (ORR) was also higher with the addition of daratumumab: 84% vs 63%, as were other parameters: ≥VGPR = 62% vs. 29% and ≥CR = 26% vs 10%; (P< 0.0001). MRD-negativity correlated with prolonged PFS and rate of death was 15% (DVd) vs. 24% (Vd), with thrombocytopenia the most commonly reported AE inn both subsets; no new safety data was added.
Both the CASTOR and POLLUX trials were also assessed for outcome via high-risk status and the data was presented in a poster by Katja C. Weisel from the University Hospital of Tuebingen in Germany. In order to classify patients for high-risk (defined by the presence of one or more of the following abnormalities: t(4;14), t(14;16), or del17p), bone marrow aspirates were assessed via next generation sequencing (NGS); patients lacking these abnormalities were considered standard risk. From the POLLUX trial, 311 patients were assessed via NGS, with a median follow-up of 17.3 months. DRd led to significantly longer PFS and higher ORR than Rd, with DRd treatment of high-risk patients bringing the PFS back to a level comparable to treatment of standard risk patients with Rd. For the CASTOR trial, the addition of daratumumab to bortezomib and dexamethasone led to an improved outcome (in terms of ORR, CR and VGPR) for high-risk patients, bringing these parameters back to a similar level as that of standard-risk patients. In conclusion, the addition of daratumumab to the standard regimens of either lenalidomide and dexamethasone or bortezomib and dexamethasone, led to improved outcomes across both high-risk and standard-risk subsets. Please also refer to the video of Katja C. Weisel talking to the MM Hub during the 2017 ASCO Annual Meeting.
In summary, daratumumab has been extensively tested in RRMM patients with different drug regimens, giving extremely positive outcomes and providing a viable late stage therapy for these heavily pre-treated patients. Further clinical trials for RRMM patients are currently recruiting, but it will also be interesting to see data for daratumumab as a potential frontline regimen.