Efficacy and safety of the BNT162b2 mRNA COVID-19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial.

INTRODUCTION: Individuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months' follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine. PATIENTS AND METHODS: Between July 2020-January 2021, 46,429 participants aged ≥ 12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥ 16 years for safety and ≥ 12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up. RESULTS: At baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months' follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4(BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported. CONCLUSION: In participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer. Clinical trial number: NCT04368728.

Recent Advances in the Management of Smoldering Multiple Myeloma.

There is remarkable progress in the treatment of multiple myeloma (MM) with significant improvement in survival in the past 10 years. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) can evolve into symptomatic multiple myeloma (sy-MM) with organ involvement. SMM has associated with a much higher progression to MM compared to MGUS. In 2014, International Myeloma Working Group (IMWG) reclassified ultra-high-risk smoldering myeloma patients with bone marrow plasma cells > 60% or serum-free light chain ratio (FLCr) > 100 or > 1 focal bone lesion on the magnetic resonance imaging as MM. SMM is a heterogeneous disorder with probability for progression to myeloma up to 50% in the first 5 years. Several risk models and clinical features have been identified to stratify the risk of progression to MM. Thanks to advances in our understanding of the genomic profile of MM, there are several ongoing clinical trials, and genomic studies are being done to assess the risk of progression to MM and early intervention. There is still no standard criterion regarding when to start therapy. This review discusses identifying SMM patients who are at high risk of progression to sy-MM and recent development of new and early treatment strategies and ongoing clinical trials for these high-risk SMM patients.

Clinical Resolution of Red Cell Aplasia Associated del 17p Multiple Myeloma, When Treated With Bortezomib and Dexamethasone.

Red cell aplasia has been rarely described in association with multiple myeloma. We present a case of a 79-year-old female, who was initially diagnosed with iron deficiency anemia, which did not improve with iron supplementation and required blood transfusions. Bone marrow biopsy showed red cell aplasia associated with kappa light chain multiple myeloma with 14.8% plasma cells. Further tests showed 0.35 g/dL M protein, and kappa/lambda ratio was 131.84. Cytogenetic showed deletion 13q, deletion 17p, loss of 1p and gain of chromosome 5. Multiple myeloma directed treatment with bortezomib and dexamethasone was initiated. Patient had clinical resolution of anemia and did not require further blood transfusions. This is an intriguing case of red cell aplasia associated with poor risk multiple myeloma (del 17p), which showed clinical improvement in anemia with bortezomib-based therapy. This case highlights the role of clonal plasma cells proliferation in the pathogenesis of red cell aplasia as myeloma directed treatment helped patient to become transfusion independent.

Keratinocyte growth factor.

Mucositis occurs in over 90% of patients undergoing stem cell transplantation for hematological malignancies. It is associated with significant morbidity in the form of pain, dysphagia and decreased oral intake, as well as mortality. Palifermin is a recombinant keratinocyte growth factor that has been shown to be effective in decreasing the incidence, severity and duration of mucositis in Phase III trials. Improvement in patient functioning during hematopoietic stem cell transplants has also been reported. This review deals with the preclinical data and the clinical trials that have been carried out with this agent in patients with hematologic malignancies. In addition limited Phase I and II data on solid tumors is available and will be included.

Treatment options for metastatic renal cell carcinoma: a review.

Metastatic renal cell carcinoma (RCC) has a poor overall survival. Localized RCC remains a surgical disease. About 20%-30% patients who present with limited disease at the time of nephrectomy develop metastasis. The median time to relapse after nephrectomy is 15-18 months. The maximum numbers of relapses are within the first 3 years. In metastatic RCC, immunotherapy is effective in a relatively small percentage of patients but is very toxic. In recent years, there has been an improved understanding of the biology of RCC. This has lead to the development of various agents that target ligands at the molecular level. The hypoxia inducible factor-alfa (HIF-)/ vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) signal transduction pathway are targets for some of these novel agents. Recent randomized phase III trials have shown an improved outcome in patients with metastatic disease who received these targeted agents. This review deals with management of advanced and metastatic renal cell cancer with an emphasis on recently developed targeted therapies.