Year in Review: Hematologic Malignancies – MedPage Today

The year in hematologic malignancy management was punctuated by the deadly COVID-19 pandemic, a flurry of FDA approvals ushering in new therapies, and continued steady advances in cellular products and other treatments for leukemia, lymphoma, multiple myeloma, and other cancers of the blood.

COVID-19 Especially Risky in Blood Cancer

No story in 2020 dominated the news more than the COVID-19 pandemic, and early data emerged suggesting the virus was particularly deadly in patients with hematological cancers.

Further studies confirmed these initial findings, showing that patients with hematologic malignancies had an increased risk of hospitalization (HR 2.49, 95% CI 1.35-4.67) compared to those with solid tumors, and a potentially higher risk for severe illness as well (HR 1.79, 95% CI 0.97-3.32).

More recent research on COVID-19 in cancer patients demonstrated that immunocompromised patients undergoing hematopoietic stem-cell transplants or chimeric antigen receptor (CAR) T-cell therapy shed viable SARS-CoV-2 virus for longer periods than had been previously reported, with one patient remaining infectious over 2 months after symptom onset.

FDA Keeps Busy

Several new agents saw first-time approvals in 2020.

Relapsed or refractory mantle cell lymphoma (MCL) got its first CAR T-cell therapy with the approval of brexucabtagene autoleucel (Tecartus), following impressive results from the ZUMA-2 trial.

FDA okayed a new oral formulation of decitabine and cedazuridine (Inqovi) for certain adults with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia. Another oral chemotherapy agent -- azacitidine (Onureg) -- was also approved for acute myeloid leukemia (AML) patients in first remission who are unable to continue intensive therapy.

Overcoming reservations due to a novel toxicity, FDA granted accelerated approval to belantamab mafodotin (Blenrep) for heavily pretreated multiple myeloma, marking the first therapy that targets B-cell maturation antigen in any disease. Due to the risk of ocular toxicity, prescribing information will include a boxed warning and the drug will be distributed through a Risk Evaluation and Mitigation Strategy.

Also in myeloma, the CD38-targeted drug isatuximab (Sarclisa) gained approval as a third- or later-line option in relapsed and refractory disease.

Tafasitamab (Monjuvi) was granted accelerated approval for adults with difficult-to-treat diffuse large B-cell lymphoma (DLBCL). The CD19-targeted cytolytic antibody is approved in combination with lenalidomide (Revlimid) for patients ineligible for autologous stem-cell transplantation.

CAR T-Cell Therapy

Continued progress in CAR T-cell therapy and other cellular products was reported in 2020. In patients with anti-CD19-resistant acute B-cell leukemia, salvage treatment with an anti-CD22 CAR-T product led to complete responses in 70% of patients.

Seeking to reduce a common side effect of CAR T-cell therapy -- cytokine release syndrome (CRS) -- a prospective cohort study showed a 50% decline in CRS when patients received risk-adapted preemptive treatment with tocilizumab (Actemra).

A small pilot study involving about a dozen patients with relapsed or refractory lymphoma or leukemia showed promising results with a therapy using allogeneic natural killer (NK) cells engineered to express anti-CD19 CAR, and reported no major toxicities.

Impressive results with CAR T-cell treatments were also also reported in Hodgkin's lymphoma, multiple myeloma, aggressive lymphomas, and indolent non-Hodgkin's lymphoma.

Leukemia

In a head-to-head phase III trial in China, dasatinib (Sprycel) outperformed imatinib (Gleevec) for survival in kids with Philadelphia chromosome-positive acute lymphoblastic leukemia, and proved superior in other oncologic outcomes.

At the Transplantation and Cellular Therapy Meetings, two studies focused on improving transplant in AML. In one study, myeloablative conditioning led to a long-term survival benefit versus reduced-intensity conditioning in patients treated with allogeneic hematopoietic stem-cell transplant (HSCT). A second study showed that using a radiolabeled anti-CD45 antibody can increase rates of allogeneic HSCT in older patients with relapsed or refractory disease.

Finally, a study presented at the European Hematology Association (EHA) congress confirmed the benefit of adding the BCL-2 inhibitor venetoclax (Venclexta) to a standard therapy for older patients with AML, adding a median 5 months in overall survival over azacitidine alone.

Lymphoma

An international phase III trial established a potential new standard regimen in pediatric B-cell lymphoma. The study showed that adding rituximab (Rituxan) to standard lymphomes malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B-cell lymphoma significantly improved event-free survival (EFS) and overall survival (OS). EFS rates at 3 years were 93.9% with rituximab compared to 82.3% with LMB alone (HR 0.32, 95% CI 0.15-0.66), while OS at 3 years was 95.1% versus 87.3%, respectively (HR 0.36, 95% CI 0.16-0.82).

In early-stage, unfavorable-risk classical Hodgkin's lymphoma, nivolumab (Opdivo) monotherapy led to complete remissions in over 50% of patients. And the PD-1 blocker combined with doxorubicin, vinblastine, and dacarbazine (AVD) yielded responses in nearly all patients, results of a phase II study showed.

A head-to-head trial in transplant-ineligible Hodgkin's lymphoma yielded significantly improved progression-free survival (PFS) with pembrolizumab (Keytruda) over brentuximab vedotin (Adcetris). Among 300 patients in the phase III trial, median PFS reached 13.2 months with the PD-1 immune checkpoint inhibitor pembrolizumab, as compared with 8.3 months with brentuximab vedotin, an antibody-drug conjugate (HR 0.65, 95% CI 0.48-0.88).

In Burkitt lymphoma, a less toxic, dose-adjusted regimen of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) showed efficacy in a study of 113 adults with low- or high-risk disease.

Multiple Myeloma

New research on selinexor (Xpovio), presented at the American Society of Clinical Oncology (ASCO) meeting, confirmed the XPO1 inhibitor's benefit in relapsed and refractory multiple myeloma. In the phase III BOSTON trial, adding selinexor to weekly bortezomib (Velcade) plus dexamethasone improved PFS over standard twice-weekly dosing of bortezomib plus dexamethasone alone (13.9 vs 9.5 months; HR 0.70, 95% CI 0.53-0.93).

Another study presented at ASCO confirmed a standard upfront regimen for newly diagnosed, standard- and intermediate-risk disease. In the phase III ENDURANCE trial of over 1,000 patients, median PFS was no different for those assigned to bortezomib, lenalidomide, and dexamethasone compared with those receiving carfilzomib (Kyprolis), lenalidomide, and dexamethasone (HR 1.04, 95% CI 0.83-1.31).

Findings presented at the EHA congress also suggested a potential maintenance option for newly diagnosed patients ineligible for stem-cell transplant and a possible new treatment regimen -- isatuximab, carfilzomib, and dexamethasone -- in the relapsed and refractory setting.

Other recent developments in hematologic cancers:

Last Updated December 08, 2020

Ian Ingram joined MedPage Today in 2018 as Deputy Managing Editor, and covers oncology for the site.

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Year in Review: Hematologic Malignancies - MedPage Today