Issue Archive

BCR::ABL1-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, prefibrotic myelofibrosis, and primary myelofibrosis, are clonal hematologic malignancies caused by a proliferation of stem cells harboring mutations that activate the JAK-STAT pathway. Several scoring systems have been developed to direct management and consideration for stem cell transplantation based on the risk of disease-associated morbid events or evolution. Pasquer and coauthors present an overview of MPN disease evolution and compare the scoring systems to propose a subtype-specific algorithm for the best application of these scores.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive curable malignancy, but older patients are at high risk of disease relapse because they either are unable to tolerate full-intensity chemoimmunotherapy or have comorbid conditions limiting therapy. With an ever-increasing number of novel therapies, it has become challenging to determine what to offer older individuals with relapsed or refractory DLBCL. Based on 2 illustrative cases, Wallace and colleagues discuss their approach to the options for this population, incorporating functional assessment in deciding among chimeric antigen receptor T-cell therapies, bispecific antibodies, and novel agents.

In the era of targeted therapy, the treatment of advanced classical Hodgkin lymphoma (cHL) has changed, moving away from traditional chemotherapy. Combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine improved survival compared to ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) but increased adverse events. In this month’s CME article, Lee et al report on a phase 2 trial replacing vinblastine with nivolumab in 57 patients with bulky stage II or stage III/IV cHL. Complete response and progression-free survival rates were both 88% at a median follow-up of 24.2 months, with a favorable safety profile. This suggests that further evaluation of combined programmed death receptor 1 inhibition and CD30 antibody–drug combination regimens for frontline advanced stage cHL is warranted.

Badros et al report results of a phase 3 trial evaluating daratumumab plus lenalidomide (D-R) vs lenalidomide alone (R) for maintenance therapy in 200 patients with multiple myeloma (MM) who are anti-CD38 therapy–naïve and minimal residual disease (MRD)–positive after transplant. MRD-negativity conversion at 12 months was significantly higher with D-R (50.5% vs 18.8%). D-R appears superior to R alone for maintenance posttransplant in this population, although the role of D-R will need continuous evaluation in the era where most patients now receive D therapy as part of initial induction therapy.

Class I HLA alterations are frequent in lymphoma and may interfere with immunotherapy by abrogating HLA-dependent T-cell responses. Kwang and colleagues used targeted DNA sequencing to examine HLA class I in cutaneous T-cell lymphomas (CTCL), revealing abnormalities in 40% of 65 patients with mycosis fungoides or Sézary syndrome. HLA abnormalities are frequently subclonal, change over time, and are associated with worse progression-free survival. Surprisingly, the changes are not associated with overall reduction in total class I HLA expression. The dynamic changes in HLA expression may be important for understanding the effects of immunotherapy in CTCL.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant disorder. Visram et al examined whether the outcome of MGUS is different if it is found by routine screening or during evaluation for something else. The authors compared outcomes of 379 screened MGUS cases from a population-based study to those of 1384 patients diagnosed during routine clinical evaluation. With a median follow-up of the screened and clinical cohorts of 26 years and 40 years respectively, the cumulative incidence of progression was similar in the 2 populations. Ongoing studies to determine whether early treatment has an impact on survival will determine whether universal screening is indicated.

Red blood cell (RBC) alloimmunization is a vexing problem in sickle cell disease (SCD), but the immune predisposing mechanism is unclear. Su and colleagues profiled the humoral immune response in SCD mice to T-cell–dependent and T-cell–independent (TI) antigens. SCD mice displayed enhanced type 2 TI (TI-2) responses mediated by type I interferons (IFN-I). The increased TI-2 responses were associated with increased B-1b cells (B-1 cells in humans), a B-cell subset that responds to TI-2 antigens; B-1 cells are also increased in patients with SCD. This is associated with elevated anti-RBC antibodies in both SCD mice and patients. Antibodies are abrogated in IFN-I–deficient mice. Though focused on autoantibodies, the results may also provide insight into the high rate of alloantibody production in patients with SCD.