SUMMARY We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations, and discovered putative tumor suppressor genes by determining homozygous deletions and loss-of-heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53 and DIS3 (particularly in non-hyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g. KRAS, NRAS and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of non-mutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.

IMPORTANCE COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti-COVID-19 interventions in this at-risk population. Convalescent plasma therapy may benefit immunocompromised individuals with COVID-19, including those with hematologic cancers.OBJECTIVE To evaluate the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic cancers and COVID-19 from a multi-institutional cohort. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study using data from the COVID-19 and Cancer Consortium registry with propensity score matching evaluated patients with hematologic cancers who were hospitalized for COVID-19. Data were collected between

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.

Summary Patients with relapsed/refractory multiple myeloma (RRMM) for whom the benefits of lenalidomide have been exhausted in early treatment lines need effective therapies. In cohort A of the phase 2 MM‐014 trial, we examined the safety and efficacy of pomalidomide plus low‐dose dexamethasone immediately after lenalidomide‐based treatment failure in patients with RRMM and two prior lines of therapy. Pomalidomide 4 mg was given on days 1 to 21 of 28‐day cycles. Dexamethasone 40 mg (20 mg for patients aged >75 years) was given on days 1, 8, 15 and 22 of 28‐day cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints included progression‐free survival (PFS), overall survival (OS) and safety. The intention‐to‐treat population comprised 56 patients; all received prior lenalidomide (87·5% lenalidomide refractory) and 39 (69·6%) received prior bortezomib. ORR was 32·1% (28·2% in the prior‐bortezomib subgroup). Median PFS was 12·2 months (7·9 months in the prior‐bortezomib subgroup). Median OS was 41·7 months (38·6 months in the prior‐bortezomib subgroup). The most common grade 3/4 treatment‐emergent adverse events were anaemia (25·0%), pneumonia (14·3%) and fatigue (14·3%). These findings support earlier sequencing of pomalidomide‐based therapy in lenalidomide‐pretreated patients with RRMM, including those who have become refractory to lenalidomide. Trial registration: http://www.ClinicalTrials.gov identifier NCT01946477.