Citations

PURPOSE At the primary analysis of CASTOR (median follow-up, 7.4 months), daratumumab plus bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival versus bortezomib and dexamethasone (Vd) alone in relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the final analysis for overall survival (OS). METHODS CASTOR was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned to Vd (up to eight cycles) with or without daratumumab (until disease progression). After positive primary analysis and protocol amendment, patients receiving Vd were offered daratumumab monotherapy after disease progression. RESULTS At a median (range) follow-up of 72.6 months (0.0-79.8), significant OS benefit was observed with D-Vd (hazard ratio, 0.74; 95% CI, 0.59 to 0.92; P = .0075). Median OS was 49.6 months with D-Vd versus 38.5 months with Vd. Prespecified subgroup analyses demonstrated an OS advantage with D-Vd versus Vd for most subgroups, including patients age ≥ 65 years and patients with one or two prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and prior bortezomib treatment. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Vd versus Vd were thrombocytopenia (46.1% v 32.9%), anemia (16.0% v 16.0%), neutropenia (13.6% v 4.6%), lymphopenia (10.3% v 2.5%), and pneumonia (10.7% v 10.1%). CONCLUSION D-Vd significantly prolonged OS in patients with RRMM, with the greatest OS benefit observed in patients with one prior line of therapy. To our knowledge, our results, together with the OS benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrate for the first time an OS benefit with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02136134 [CASTOR]).

Few guidelines exist for COVID-19 vaccination amongst cancer patients, fostering uncertainty regarding the immunogenicity, safety, and effects of cancer therapies on vaccination, which this review aims to address. A literature review was conducted to include the latest articles covering the immunogenicity and safety of COVID-19 vaccination in patients with solid and hematologic cancers receiving various treatments. Lower seropositivity following vaccination was associated with malignancy (compared to the general population), and hematologic malignancy (compared to solid cancers). Patients receiving active cancer therapy (unspecified), chemotherapy, radiotherapy, and immunosuppressants generally demonstrated lower seropositivity compared to healthy controls; though checkpoint inhibition, endocrine therapy, and cyclin dependent kinase inhibition did not appear to affect seropositivity. Vaccination appeared safe and well-tolerated in patients with current or past cancer and those undergoing treatment. Adverse events were comparable to the general population, but inflammatory lymphadenopathy following vaccination was commonly reported and may be mistaken for malignant etiology. Additionally, radiation recall phenomenon was sporadically reported in patients who had received radiotherapy. Overall, while seropositivity rates were decreased, cancer patients showed capacity to generate safe and effective immune responses to COVID-19 vaccination, thus vaccination should be encouraged and hesitancy should be addressed in this population.