News

Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia

Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population—although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug–drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.

Prof Anne Bergeron, MD,Prof Malgorzata Mikulska, MD, Julien De Greef, MD, Louise Bondeelle, MD, Prof Tomas Franquet, MD, Prof Jean-Louis Herrmann, PharmD, et al.

© 2022 Elsevier Ltd. All rights reserved.

Leukemia

Venetoclax and acute myeloid leukaemia: an expanding new frontier

Venetoclax is an inhibitor of the anti-apoptotic B-cell lymphoma-2 (BCL-2) protein that has revolutionised the management of acute myeloid leukaemia in the past 5 years. Venetoclax in combination with azacitidine has become the new standard of care for the majority of patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy due to age, fitness, or comorbidities. 1 Venetoclax has improved outcomes for this patient population and represents a valuable new treatment option in this setting. There is now interest in studying venetoclax combined with other acute myeloid leukaemia treatment regimens, including intensive chemotherapy.

Kieran D Sahasrabudhe , Alice S Mims.

© 2022 Elsevier Ltd. All rights reserved.

Leukemia

Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease

Gene therapy with LentiGlobin for sickle cell disease (bb1111, lovotibeglogene autotemcel) consists of autologous transplantation of a patient’s hematopoietic stem cells transduced with the BB305 lentiviral vector that encodes the βA-T87Q-globin gene. Acute myeloid leukemia developed in a woman approximately 5.5 years after she had received LentiGlobin for sickle cell disease as part of the initial cohort (Group A) of the HGB-206 study. An analysis of peripheral-blood samples revealed that blast cells contained a BB305 lentiviral vector insertion site. The results of an investigation of causality indicated that the leukemia was unlikely to be related to vector insertion, given the location of the insertion site, the very low transgene expression in blast cells, and the lack of an effect on expression of surrounding genes. Several somatic mutations predisposing to acute myeloid leukemia were present after diagnosis, which suggests that patients with sickle cell disease are at increased risk for hematologic malignant conditions after transplantation, most likely because of a combination of risks associated with underlying sickle cell disease, transplantation procedure, and inadequate disease control after treatment. (Funded by Bluebird Bio.)

Sunita Goyal, M.D., John Tisdale, M.D., Manfred Schmidt, Ph.D., Julie Kanter, M.D., Jennifer Jaroscak, M.D., Dustin Whitney, Ph.D., Hans Bitter, Ph.D., Philip D. Gregory, Ph.D., Geoffrey Parsons, Ph.D., Marianna Foos, M.S., Ashish Yeri, Ph.D., Maple Gioia, A.L.M., et al.

This article was published on December 12, 2021, at NEJM.org.

Leukemia

Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia

Hairy-cell leukemia (HCL) is a CD20+ indolent B-cell cancer in which a BRAF V600E kinase–activating mutation plays a pathogenetic role. In clinical trials involving patients with refractory or relapsed HCL, the targeting of BRAF V600E with the oral BRAF inhibitor vemurafenib led to a response in 91% of the patients; 35% of the patients had a complete response. However, the median relapse-free survival was only 9 months after treatment was stopped.

Methods

In a phase 2, single-center, academic trial involving patients with refractory or relapsed HCL, we assessed the safety and efficacy of vemurafenib (960 mg, administered twice daily for 8 weeks) plus concurrent and sequential rituximab (375 mg per square meter of body-surface area, administered for 8 doses over a period of 18 weeks). The primary end point was a complete response at the end of planned treatment.

Results

Among the 30 enrolled patients with HCL, the median number of previous therapies was 3. A complete response was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been refractory to chemotherapy (10 patients) or rituximab (5) and all those who had previously been treated with BRAF inhibitors (7) had a complete response. Thrombocytopenia resolved after a median of 2 weeks, and neutropenia after a median of 4 weeks. Of the 26 patients with a complete response, 17 (65%) were cleared of minimal residual disease (MRD). Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months; relapse-free survival among the 26 patients with a response was 85% at a median follow-up of 34 months. In post hoc analyses, MRD negativity and no previous BRAF inhibitor treatment correlated with longer relapse-free survival. Toxic effects, mostly of grade 1 or 2, were those that had previously been noted for these agents.

Conclusions

In this small study, a short, chemotherapy-free, nonmyelotoxic regimen of vemurafenib plus rituximab was associated with a durable complete response in most patients with refractory or relapsed HCL.

 Enrico Tiacci, M.D., Luca De Carolis, M.D., Edoardo Simonetti, M.D., Monia Capponi, M.D., Achille Ambrosetti, M.D., Eugenio Lucia, M.D., Agostino Antolino, M.D., Alessandro Pulsoni, M.D., Samantha Ferrari, M.D., Pier L. Zinzani, M.D., Stefano Ascani, M.D., Vincenzo M. Perriello, M.D., et al.

Leukemia