New Standards Are Emerging for Follicular Lymphoma and CLL

Christin Melton, ELS | March 20, 2017
Krishna V. Komanduri, MD

Krishna V. Komanduri, MD

Non-Hodgkin lymphoma (NHL) encompasses several hematological malignancies, which are broadly categorized as indolent or aggressive. Low-grade lymphomas, which typically progress slowly, include follicular lymphoma (FL), mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and marginal zone lymphoma. Indolent NHL has the potential to transform to aggressive or high-grade lymphoma, which is one reason controlling indolent disease remains such a priority.

In an OncLive Peer Exchange® discussion led by Krishna V. Komanduri, MD, experts in hematological malignancies reviewed the evolving paradigm for managing indolent NHL. “The past few years have been incredibly exciting in terms of improving our understanding of lymphoma biology and developing novel approaches for treatment,” Komanduri said.

Follicular Lymphoma

Patients with FL are often asymptomatic and their condition is discovered incidentally during a routine examination or workup for another health problem. Leo I. Gordon, MD, explained that most patients whose disease presents this way do not require treatment until the lymphoma progresses. “There are no data that suggest earlier treatment offers a survival advantage,” he said.

First-Line Options

When treatment is required, physicians must decide whether to use a regimen that includes chemotherapy. Gordon said data increasingly show patients with less aggressive FL derive similar benefits from less toxic, chemotherapy-free regimens. Historically, the most common choice is single- agent rituximab (Rituxan). He said data presented at the 2016 American Society of Hematology Annual Meeting suggest that “the addition of lenalidomide [Revlimid]... might offer a response and complete response [CR] advantage.” An immuno- modulatory agent, lenalidomide is approved for various types of lymphoma but not for FL. The randomized phase II SAKK 35/10 trial (Table 1) compared rituximab monotherapy versus rituximab plus lenalidomide.1 The combination was associated with higher rates of CR/unconfirmed CR, CR at 30 months, and longer time to next treatment.

 

Table 1. Outcomes in the Phase II SAKK 35/10 Trial

CR indicates complete response; CRu, complete response unconfirmed; n/a, not applicable; NR, not reached; OS, overall survival; PFS, progression-free survival.

Gordon said several options are available for patients who need more intensive therapy. Typical regimens are R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and BR (rituximab plus bendamustine [Treanda]). Although studies show BR is less toxic than R-CHOP, Gordon expressed unease about the lack of long-term data for BR. “My concern is that we may begin to see certain malignancies occurring in patients treated with BR,” he said.

Komanduri asked panelists about the role for consolidation and maintenance in FL. John P. Leonard, MD, said that, while studies have found rituximab or obinutuzumab (Gazyva) maintenance therapy prolongs progression-free survival (PFS), they have not shown improvement in overall survival. He noted that the RESORT study reported similar outcomes for patients who received maintenance rituximab and patients retreated with rituximab after progression.

Leonard said maintenance was essentially prolonging 4 to 6 months of treatment into 2.5 years of treatment, with no survival benefit and greater toxicity. He stressed the importance of ensuring that patients understand maintenance therapy’s risks and limited benefits.

Relapsed or Refractory Follicular Lymphoma

“The nature of this disease is that we don’t cure patients and they have multiple relapses,” Komanduri said. Several options are available for relapsed or refractory FL, leaving hematologists to wrestle with how best to sequence therapy. Gordon said Follicular Lymphoma International Prognostic Index scores, molecular analysis, or time to recurrence can help identify patients who are apt to respond poorly to second-line options. Recurrence within 12 to 24 months of first-line therapy is an especially strong predictor of poor response to subsequent therapy. Gordon recommended considering a clinical trial of a novel therapy or a transplant, when feasible, for high-risk patients.

Patients whose FL recurs after 24 months of remission are considered treatment sensitive. Leonard said, “you can do whatever you want” for such patients. Options for relapsed or refractory FL include bendamustine monotherapy, BR, a fludarabine-based regimen, radioimmunotherapy, single-agent rituximab, or bendamustine plus obinutuzumab.


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