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Clinical Trial Results Leave Treatment Questions Unanswered for Certain Lymphomas

Lawrence D. Kaplan, M.D., discusses recent updates and next steps to be taken in Hodgkin, mantle cell and follicular lymphoma.
 
BY Kristie L. Kahl
PUBLISHED November 13, 2018
The treatment landscape for certain blood cancers, such as Hodgkin, mantle cell and follicular lymphomas, is an expanding paradigm – one patients may want to keep up to date with.

In particular, Lawrence D. Kaplan, M.D., noted that questions remain about treatment options for these cancers now that various clinical trial results have been presented.

Kaplan, who is a clinical professor of medicine and director of the Adult Lymphoma Program in the Division of Hematology-Oncology at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, sat down with OncLive – a sister publication of CURE – to discuss recent updates and next steps to be taken in Hodgkin, mantle cell and follicular lymphoma.

Hodgkin Lymphoma

In March, the Food and Drug Administration (FDA) approved Adcetris (brentuximab vedotin) for use in combination with chemotherapy as a frontline treatment for adult patients with stage 3 or 4 classical Hodgkin lymphoma based on findings from the global phase 3 ECHELON-1 trial. The trial – designed to evaluate Adcetris combined with doxorubicin, vinblastine and dacarbazine (A+AVD) – showed superior progression-free survival among patients treated with the Adcetris regimen compared with standard chemotherapy.

In the initial results, the Adcetris combination demonstrated a 5.1 percent benefit in two-year modified progression-free survival, or noncomplete responses after completion of frontline therapy) over standard chemotherapy, of which a subgroup analysis of the North American population revealed an absolute difference of 10.6 percent. Lastly, an 11.7 percent difference was found in progression-free survival per investigator review at two years.

However, Kaplan noted the skepticism that surrounds Adcetris: modified progression-free survival is not a standard endpoint for clinical trials, and the agent has yet to demonstrate a benefit in overall survival.

“The study has been criticized though, and I would tend to agree,” he said. “…At present, I don’t really suggest this regimen. The National Comprehensive Cancer Network has reviewed it and is also not quite on board.”

Mantle Cell Lymphoma

The Bruton kinase (BTK) inhibitors Imbruvica (ibrutinib) and Calquence (acalabrutinib) have shown promise in the treatment of relapsed/refractory mantle cell lymphoma, and have the potential to substantially evolve in the coming years. Currently, both agents are approved for patients who have had one or more previous lines of therapy.

However, Kaplan noted that the next steps for researchers are to expand on this progress.

“(Imbruvica and Calquence have) also been looked at in chronic lymphocytic leukemia. The major endpoint here is looking at minimal residual disease (the small number of cancer cells from the bone marrow during and after treatment or in remission),” he said. “It looks like this combination does improve minimal residual disease negativity. The question remains whether this will result in survival benefit.”

Follicular Lymphoma

Like its disease counterparts, combination regimens are also being explored for the treatment of follicular lymphoma – in particular with Rituxan (rituximab) and the chemotherapy agent Bendamustine. “It’s been shown in phase 2 studies, and it was the subject of a 1,000-patient international trial,” Kaplan explained.

In the trial, patients received Revlimid (lenalidomide) plus Rituxan or Revlimid and chemotherapy – which is the standard of care in this patient population; however, it failed to show superiority with Revlimid and Rituxan over chemotherapy.

“It was a superiority trial, and the attempt was being made to indicate that rituximab was superior to chemotherapy,” Kaplan said. “Those who designed the trial had high expectations, and as a result, the superiority idea should have been done differently. It looks like the outcomes were similar.”

This was adapted from an original article published on OncLive as, “UCSF Expert Highlights Progress in Lymphoma Landscape.”
 
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