Leo I. Gordon MD
Clinical updates in Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) have continued to evolve the space, such as moving away from toxic regimens and more toward a personalized or chemotherapy-free approach, explained Leo I. Gordon, MD.
For example, in Hodgkin lymphoma, the randomized, phase III ECHELON-1 trial compared brentuximab vedotin (Adcetris) plus doxorubicin, vinblastine, and dacarbazine (A+AVD) with AVD plus bleomycin (ABVD) in 1334 patients with newly diagnosed, advanced Hodgkin lymphoma. Results showed that treatment with A+AVD led to a 23% reduction in the risk of progression, death, or initiation of new therapy, leading to the FDA approval in this patient population in March 2018.1
However, the brentuximab vedotin regimen should not be a one-size-fits-all approach for patients, said Gordon, the Abby and John Friend Professor of Oncology Research, and professor of medicine (hematology and oncology), at Feinberg School of Medicine, Northwestern University. Checkpoint inhibition, he said, is continuing to be explored in various settings of the disease. In NHL, chemotherapy-free regimens continue to garner interest, specifically for patients with follicular lymphoma or low-grade lymphoma.
Results from the phase III RELEVANCE study showed that the combination of lenalidomide (Revlimid) and rituximab (Rituxan; R2
) were found to have similar efficacy outcomes compared with rituximab plus chemotherapy in treatment-naïve patients with follicular lymphoma.2
But beyond those data, investigators are looking into other frontline combination regimens, such as ibrutinib (Imbruvica), lenalidomide, and rituximab. A key challenge in the field, Gordon noted, is figuring out what to do for patients who relapse within 2 years of ending therapy.
In an interview during the 2019 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Gordon discussed these recent updates in Hodgkin lymphoma and NHL and pointed to research on the horizon.
OncLive: What are the key changes in Hodgkin lymphoma and NHL treatment?
: The [2 main] issues in Hodgkin lymphoma still remain: first, what to do with PET scans and how to improve results based on PET scans, [and second, answering] the question, “Where are we going in the future?”
In NHL, I reviewed data mostly on follicular lymphoma or low-grade lymphoma; I focused on initial therapy, new combinations, a trend toward moving away from chemoimmunotherapy. [There have been] data on the use of immunomodulatory (IMiD) agents, such as lenalidomide. The question of what to do in second-line therapy relates to the use of novel agents, chemoimmunotherapy, and the PI3K inhibitors, in which there is interest. Data [have been reported] on a new dual-PI3k inhibitor, copanlisib (Aliqopa).
A burning question in low-grade lymphoma, especially follicular lymphoma, is what to do with patients who relapse within 24 months of initial therapy. That appears to be a fairly high-risk group, with [data suggesting] that those patients don’t do very well. The questions are, “What do we do upfront?” and “What do we do at the time of first relapse?”
Going back to Hodgkin lymphoma, could you discuss the impact of the FDA approval of the A+AVD regimen?
First of all, that has become the new control arm of an upcoming study that will compare brentuximab vedotin plus AVD with nivolumab (Opdivo), so we are introducing the checkpoint inhibitors in upfront treatment of [patients with] Hodgkin lymphoma. At our institution, we have not identified [A+AVD] as the [standard] frontline therapy yet. However, for the group of patients we think are at risk for pulmonary toxicity from bleomycin, it is a reasonable regimen. Whether [this regimen] should replace ABVD as the standard, I’m not certain yet. The North American subgroup analysis suggests that, once again, brentuximab vedotin offers better progression-free survival (PFS) compared with bleomycin.
We are trading some toxicity, so patients getting brentuximab vedotin have more neutropenia and febrile neutropenia, and they require the use of a growth factor, which isn’t needed with ABVD. I’m concerned whether that will have long-term effects. I also have concerns about the every-2-week use of pegfilgrastim (Neulasta) for 6 cycles or 12 doses in young patients, so unless someone has a significant risk for pulmonary toxicity, we are still using ABVD as our standard.
Have new data with checkpoint inhibitors come out in this space?
We are excited about the use of the checkpoint inhibitors. We did a study years ago on adjuvant [immunotherapy] in [patients with] diffuse large B-cell lymphoma (DLBCL) following autologous stem cell transplant with a checkpoint inhibitor; that was pidilizumab, which is no longer being used. Therefore, we have reasons to think, especially in Hodgkin lymphoma, that [these drugs] are going to be active.