From the Journals

Novel therapies may expand anti-MZL toolbox



Potential new treatment options for patients with advanced marginal zone lymphomas include targeted therapies, immunomodulators, proteasome inhibitors, and radioimmunotherapy, Italian investigators reported.

Current treatment options for patients with MZL include antibiotics, radiotherapy, and single-agent immunotherapy, commonly with the CD20 inhibitor rituximab. For patients with localized, early stage disease, these therapies are often highly effective and capable of producing long-term remission, but there is no standard of care for patients with disseminated nodal or extranodal disease, wrote Pier Luigi Zinzani, MD, PhD, and Alessandro Broccoli, MD, of the University of Bologna, Italy.

“Several targeted agents have demonstrated their efficacy, with generally mild and reversible side effects, in patients with MZL, although clinical trials specifically involving this kind of subjects are lacking due to the rarity of the disease. Newer molecules targeting specific intracellular pathways involved in tumor proliferation, cell differentiation, motility and apoptosis represent attractive alternatives to conventional cytotoxic drugs and deserve further investigation,” they wrote in a review article (Best Pract Res Clin Haematol. 2017;30[1-2]:149-57).

They cited a study showing that single-agent lenalidomide (Revlimid), an immunomodulator that has become a mainstay of therapy for multiple myeloma, was associated with a 61% overall response rate (ORR), including 33% complete responses (CR) in patients with non–gastric mucosa–associated lymphoid tissue (MALT) lymphoma, or gastric MALT lymphoma that was either negative for Helicobacter pylori or was Helicobacter pylori positive but refractory to antibiotics (Haematologica 2013;98:353-6).

Lenalidomide plus rituximab was associated with an 89% ORR and 67% CR rate in patients with MZL enrolled in a clinical trial of patients with untreated advanced stage non-Hodgkin lymphomas.

Lenalidomide’s frequent partner, the proteasome inhibitor bortezomib (Velcade), has been tested alone in small studies in patients with MALT lymphoma, with one study showing an ORR of 80% in 16 patients with MALT lymphoma, although investigators noted an unexpectedly high rate of toxicities. In a different study, bortezomib was associated with an ORR of 48%, including nine CR and five partial responses in 29 patients with relapsed/refractory MALT lymphoma.

Other potential therapeutic options for patients with MZL include:

90Y-ibritumomab tiuxetan, a radiotherapeutic targeted to B-cell surface antigens, which has been associated with high CR rates and durable disease-free remissions in small series.

Obinutuzumab (Gazyva), an anti-CD20 monoclonal antibody, with data largely in other indolent lymphoma histologies.

Ibrutinib (Imbruvica), an inhibitor of Bruton’s tyrosine kinase that moderates B-cell receptor signaling, which has shown good activity against mantle cell lymphoma.

Idelalisib (Zydelig), an inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3K), with activity against indolent non-Hodgkin lymphoma.

Other agents in early stages of investigation in MZL are venetoclax, an oral B-cell lymphoma protein-2; copanlisib, an inhibitor of both the alpha and delta isoforms of PI3K; and ublituximab, an anti-CD20 monoclonal antibody that has been combined with TGR-1202, a PI3K-delta inhibitor.

“Many of these new agents show synergism when combined together and with chemotherapy or immunotherapy, without significant cumulative toxicity. Chemo-free approaches in MZL are nowadays possible and worthwhile to be pursued,” the researchers wrote.

They reported having no financial disclosures.

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