Adrienne A. Phillips, MD, MPH

Insights From the ASH 2017 Conference: Lymphoma

Question

Research being presented at this year’s American Society of Hematology (ASH) meeting suggests that brentuximab vedotin may be an effective treatment option for patients with relapsed/refractory Hodgkin lymphoma or in combination with other drugs as a first-line treatment. Do you see this drug being incorporated into standard regimens for all patients with Hodgkin lymphoma?

Answer

The jury is still out on whether brentuximab vedotin (BV) can be moved to the frontline. BV is currently indicated in classical Hodgkin lymphoma (HL) after failure of autologous stem cell transplantation (ASCT), after failure of at least 2 prior regimens in patients who are not ASCT eligible, or as consolidation after ASCT for those at high risk of progression.

The Echelon-1 study was presented at ASH 2017 during the plenary session. In this randomized multicenter phase 3 study, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) — a world standard chemotherapy approach with good outcomes and an acceptable toxicity profile — was compared with BV+AVD in 1334 previously untreated patients with advanced stage HL. The primary endpoint, modified progression-free survival (PFS), was met at 2 years (82.1% vs 77.2%; P = .007), and there was a trend towards improvement in the rate of end of treatment complete response (CR), rate of PET negativity after 2 cycles, duration of response, and event-free survival (EFS). There was no difference in overall survival (OS).

Neutropenia and febrile neutropenia were more common in the BV-AVD arm, as was severe neuropathy. A subgroup of patients received granulocyte colony-stimulating factor (G-CSF) primary prophylaxis.

A second oral abstract found that abbreviated course BV+AVD followed by involved-site radiotherapy (ISRT) was effective for early stage, unfavorable-risk HL. Though these studies have looked at the role of BV in the frontline treatment of HL, it’s too early to say if the drug should be a standard for all patients with HL.

In the Echelon-1 study, there was only a small PFS difference, the follow-up was short, and it will likely increase the cost of administration of the combination because G-CSF was used.

The authors should be applauded for achieving such results in the frontline, however, for this highly curable condition, long-term toxicity is a concern. While omitting bleomycin may reduce pulmonary toxicity, neurotoxicity may develop and it remains to be seen whether the US Food and Drug Administration (FDA) will grant this indication.

Question

What role do you see for acalabrutinib in treating mantle cell lymphoma (MCL)?

Answer

Acalabrutinib is a more selective Bruton’s tyrosine kinase (BTK) inhibitor than ibrutinib and was approved in October 2017 for relapsed MCL. Updated results from the phase 2 ACE-LY-004 study of acalabrutinib monotherapy in patients with relapsed or refractory MCL were presented at ASH 2017, showing an 81% overall response rate and a 40% CR rate.

The safety profile seems better than ibrutinib, with no atrial fibrillation in over 100 patients. The rest of the toxicity panel was similar to ibrutinib, and patients did not have to fail ibrutinib to be on the study.

We do not yet know how to sequence these agents, but it is becoming increasingly clear that the era of biological therapy is changing the therapeutic landscape of MCL, which historically has been treated with cytotoxic chemotherapy combinations.

Question

Do any studies in particular present practice-changing research for patients with follicular lymphoma (FL)?

Answer

With a prolonged life expectancy for patients with FL, a number of abstracts presented at ASH 2017 suggest less may be more for some patients. Notably, the long term follow-up of the PRIMA study of rituximab (R) maintenance after frontline R-chemotherapy failed to show a survival benefit at 10 years.

In addition, clinical practice should move away from surveillance scans in FL patients, especially in patients obtaining a CR after frontline therapy. In a retrospective, single institution study of 148 patients with documented response to front-line induction therapy, most cases of relapse in FL were detected based on clinical signs or symptoms, and there was no difference in OS between cases where relapse was first suggested on surveillance compared with those detected clinically.

Lastly, in a prospective single center study of 1050 patients with indolent lymphoma, quality of life (QoL) remained generally stable over 3 years, while emotional well-being showed improvement — suggesting that patients with this chronic disease were able to adapt to their illness over time. For those considering maintenance rituximab (PRIMA still shows a PFS benefit) and imaging (despite signs or symptoms of disease), these data may help reduce the fear and anxiety associated with relapse.

Question

In your opinion, will the Burkitt Lymphoma Genome Sequencing Project (BLGSP) help to guide treatment decisions for patients with lymphoma in the near future?

Answer

The BLGSP is an ongoing international collaborative project aimed at providing a comprehensive molecular portrait of BL across all subtypes. Nearly all cases of BL are associated with a translocation between c-MYC on the long arm of chromosome 8 and 1 of 3 locations on the immunoglobulin (Ig) genes (either with the Ig heavy chain on chromosome 14, the kappa light chain on chromosome 2, or the lambda light chain on chromosome 22).

The standard of care of BL has yet to be defined, though intensive, short-duration chemotherapy combinations are generally used for this highly aggressive disease. The BLGSP describes potentially targetable mutations in BL that may lead to more effective and less toxic treatments in the near future.

Question

Across all therapeutic areas, could you describe a few studies being presented at ASH you think are likely to be practice-changing?

Answer

Updated and new data from cellular therapy protocols dominated ASH 2017, with abstracts presented in not only malignant hematology but also benign hematology.

Tisagenlecleucel and axicabtagene ciloleucel (axi-cel; both anti-CD19 chimeric antigen receptor [CAR]-T cell therapies) were approved in 2017 for refractory acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL), respectively, and updates from the landmark clinical trials as well as in other conditions were presented.

Spectacular results were presented for a CAR-T therapy to bb2121 in patients with advanced multiple myeloma, with an 86% overall response rate to therapy in a 21-patient study. New clinical results from 2 patients in the phase 1 HGB-206 study of a sickle cell disease product — using a vector made via a refined manufacturing process — showed an improved anti-sickling effect, while data with a thalassemia product revealed durable responses in transfusion-dependent patients after up to 3 years of follow-up.

The impact of these and other studies of cellular therapy have already changed clinical practice in 2017 and will undoubtedly continue to do so into the near future.