Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched Pubmed and EMBASE up to August 20, 2020, to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of ICU admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RR), and 95% confidence intervals (CI) were calculated using a random-effects model. 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14/34 adult studies included only hospitalized patients). The risk of death amongst adult patients was 34% (95% CI 28-39, N=3240) in this sample of predominantly hospitalized patients. Patients aged >60 years had a significantly higher risk of death than patients <60 years (RR 1.82, 95% CI 1.45-2.27, N=1169). The risk of death in pediatric patients was 4% (95% CI 1-9, N=102). The RR of death comparing patients with recent systemic anti-cancer therapy to no treatment was 1.17 (95% CI 0.83-1.64; N=736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients >60 years have significantly higher mortality, and pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

The tumor suppressor p53 is often inactivated via its interaction with endogenous inhibitors mouse double minute 4 homolog (MDM4 or MDMX) or mouse double minute 2 homolog (MDM2), which are frequently overexpressed in patients with acute myeloid leukemia (AML) and other cancers. Pharmacological disruption of both of these inter-actions has long been sought after as an attractive strategy to fully restore p53-dependent tumor suppressor activity in cancers with wild-type p53. Selective targeting of this pathway has thus far been limited to MDM2-only small-molecule inhibitors, which lack affinity for MDMX. We demonstrate that dual MDMX/MDM2 inhibition with a stapled a-helical peptide (ALRN-6924), which has recently entered phase I clinical testing, produces marked antileukemic effects. ALRN-6924 robustly activates p53-dependent transcription at the single-cell and single-molecule levels and exhibits biochemical and molecular biological on-target activity in leukemia cells in vitro and in vivo. Dual MDMX/MDM2 inhibition by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and apoptosis in cell lines and primary AML patient cells, including leukemic stem cell-enriched populations, and disrupts functional clonogenic and serial replating capacity. Furthermore, ALRN-6924 markedly improves survival in AML xenograft models. Our study provides mechanistic insight to support further testing of ALRN-6924 as a therapeutic approach in AML and other cancers with wild-type p53.

Axicabtagene ciloleucel (Axi-cel) is a CD-19 Chimeric Antigen Receptor T cell therapy approved for the treatment of relapsed/refractory diffuse large B cell lymphoma. We treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients (80%) had received ≥ 3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant (AHCT). Our cohort included one patient with HIV, two patients with hepatitis B, and two patients with CNS involvement of lymphoma. Axi-cel treatment led to significant responses with 8/10 patients achieving a complete remission at 3 months, including both patients with prior CNS involvement. The treatment was generally well tolerated with 20% of patients experiencing grade ≥ 2 CRS. One patient each with HIV and hepatitis B responded without significant toxicities. In conclusion, Axi-cel led to significant efficacy with manageable toxicity in DLBCL in a real-world setting.

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