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Emerging Options for CNS Lymphomas

Emerging Options for CNS Lymphomas

Researchers are making much-needed progress in developing treatments for patients with three rare malignancies: recurrent and refractory primary central nervous system (CNS) lymphoma (PCNSL, a clinically challenging diffuse large B-cell lymphoma), secondary CNS lymphoma (SCNSL), and primary vitreoretinal lymphoma (PVRL), they reported (abstracts 7515 and 7516) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

Both studies were small, reflecting the rare nature of these diseases.

Christian Grommes, MD, of Memorial Sloan Kettering Cancer Center in New York, lead study author of one of the studies (abstract 7515), presented updated results for ibrutinib monotherapy in recurring and refractory PCNSL and SCNSL. That study team enrolled 25 adult patients, of whom 20 developed grade 3 toxicities (including lymphopenia, hyperglycemia, ALT elevation, thrombocytopenia, lung infection, AST elevation, febrile and afebrile neutropenia, urinary tract infection, colitis, and anemia). No patient deaths occurred.

At a median follow-up of 414 days, 22 patients were evaluable. Among them, the overall response rate was 68% (10 complete responses, 7 partial response), reported Grommes.

A second team described preliminary phase I maximum tolerable dose–finding results (abstract 7516) for pomalidomide treatment of relapsed/refractory PCNSL and PVRL. The study’s accrual goals were met with 29 patients enrolled, reported lead study author Han W. Tun, MD, of the Mayo Clinic in Jacksonville, Florida. Twenty-five participants were evaluable. 

The maximum tolerable dose was determined to be 5 mg daily for 21 days, every 28 days, Tun reported. The objective response rate at that dose was 40% (95% CI, 21%–61%). Four patients experienced complete responses, two patients had unconfirmed complete responses, and four patients experienced partial responses. Median progression-free survival was 5.3 months for all patients and 9 months for responders, Tun reported.

Grade 3/4 adverse events included leukopenia, neutropenia, and lymphopenia in 52% of patients, and nonhematologic toxicities in 44% of patients, including fatigue, sepsis, dyspnea, confusion, hyperglycemia, respiratory failure, and muscle weakness.

Pomalidomide is “feasible, with therapeutic activity” for both PCNSL and PVRL, Tun concluded. “It should be further evaluated for incorporation into standard induction chemoimmunotherapy, combination with immunotherapeutic agents, and maintenance therapy.”

The reports were welcome, if early, news for rare lymphomas for which cure is elusive. “These lymphomas are quite rare and there is great unmet need,” commented Barbara Pro, MD, professor of medicine at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University-Feinberg School of Medicine in Chicago. “Prognosis is quite poor.”

 
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