ASH 2016 | Immunotherapy highlights in multiple myeloma at ASH 2016

Niels van de Donk

Niels van de Donk, MD, PhD, VU University Medical Center, Amsterdam, Netherlands, discusses new immunotherapeutic strategies evaluated in multiple myeloma (MM) at the American Society of Hematology (ASH) Congress 2016 in San Diego, CA. One of the most promising is daratumumab, where two interesting updates were presented. Extended follow up of both the POLLUX (NCT02076009) and CASTOR studies (NCT02136134) showed the advantages of adding daratumumab to dexamethasone with lenalidomide or bortezomib, as well as a deeper response, which is associated with a longer survival. In addition, an unprecedentedly high percentage of minimal residual disease (MRD) negative disease has been seen in patients treated with daratumumab combinations, and these patients show very good progression-free survival (PFS). High-risk cytogenetics data in the POLLUX and CASTOR studies was also shown, with high-risk defined as deletion of del17p, as well as the translocations t(4;14) and t(14;16). In both studies, the triplet treatment combination including daratumumab was able to partially overcome the risk conferred by these high-risk cytogenetic abnormalities, and was favorable compared to doublet treatment without daratumumab, with a positive effect on PFS. Daratumumab is generally well tolerated, however transfusion-related reactions occur in around 50% of patients. It should also be noted that the first transfusion can take 6 -8 hours, which may be associated with inconvenience for patients and healthcare practitioners. An interesting development is a new subcutaneous formulation of daratumumab, which can be administered in around half an hour as it contains the hyaluronidase enzyme which creates space subcutaneously by degrading hyaluronic acid in the tissue. This formulation is also associated with a lower transfusion-related reaction rate of 24%. Additional antibodies presented were the anti-PD-L1 antibody pembrolizumab in combination with dexamethasone and pomalidomide in extensively pretreated patients, with high responses and good tolerability for this triplet treatment. However, autoimmune phenomena can occur when using checkpoint inhibitor combinations. Other interesting developments include work on CAR-T-cells such as BCMA-CARs, CD19-CARs, and upcoming APRO-CARs. He concludes that there are multiple interesting immunotherapeutic developments in multiple myeloma, which will improve patients care and patient survival.

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