NEW YORK – Relatively young patients with newly diagnosed, average-risk mantle cell lymphoma who go into remission on induction therapy face a difficult choice on their next management step: undergo immediate autologous stem cell transplantation or defer the stem cell transplant and continue on maintenance therapy.

The choice is especially difficult because both are currently considered reasonable options and each choice has certain attractions and downsides, experts highlighted in discussing this fork-in-the-road decision patients face.

Immediate autologous stem cell transplantation (ASCT) has a good chance to allow the patient to remain treatment free and in remission for as long as about 10 years, but it involves intensive upfront treatment for 6-9 months, during which the patient will likely not be able to work or carry on many usual activities. Deferring the transplant with maintenance therapy puts off this life-disrupting initial period of intensive therapy for what may be several years, but relapse on maintenance therapy is inevitable and once it happens the patient may not have as successful an outcome from an ASCT. It also means several years of ongoing drug therapy with a maintenance regimen.

“I tell my fellows that patients with newly diagnosed mantle cell lymphoma [are] one of the hardest consultations because, unlike most other lymphomas, there is no established standard therapy but a range of options,” Timothy S. Fenske, MD, said at the conference held by Imedex. “I go through the pros and cons with patients, and it comes down to the patient’s perceived quality of life and their lifestyle.”

“It’s a very difficult decision [for patients] because we don’t have the data we’d like to have,” observed Peter Martin, MD, director of the clinical research program in lymphoma at Weill Cornell Medicine, New York.

“There is a lot of upfront toxicity with transplantation, with 6-9 months out of work in my experience. Patients often tell me that they can’t afford to do that; they’ll lose their employment insurance and won’t be able to pay for replacement insurance. But then they will hopefully go 6-10 years without more treatment, which is a real benefit. With less intensive upfront treatment they have a chance for similar overall survival, but they’ll need more ongoing treatment. It’s pretty complicated and challenging” for patients to make a decision, he said. “It depends a lot on where patients are in their lives and what they are willing to accept,” Dr. Martin said.

In general, Dr. Martin took a more skeptical view of ASCT than Dr. Fenske. “There is no evidence that ASCT cures patients or prolongs their survival. It improves progression-free survival, but not necessarily overall survival,” Dr. Martin noted.

In fact, a report in December 2016 at the American Society of Hematology annual meeting (Blood. 2016 Dec 5;abstract 1095) suggested that “biology is the primary driver of outcomes in mantle cell lymphoma, not treatment,” said Dr. Martin. The results from a limited number of patients enrolled in the Nordic mantle cell lymphoma trials provided good but preliminary evidence that “if you have good biology it doesn’t matter what the treatment is, you will do well,” he explained.

In fact, a report in December 2016 at the American Society of Hematology annual meeting (Blood. 2016 Dec 5;abstract 1095) suggested that “biology is the primary driver of outcomes in mantle cell lymphoma, not treatment,” said Dr. Martin. The results from a limited number of patients enrolled in the Nordic mantle cell lymphoma trials provided good but preliminary evidence that “less intense therapy works just as well” as more intense therapy, as long as the patient has a favorable genetic profile, he explained.

In contrast, Dr. Fenske put a much more positive spin on more intensive treatment upfront with ASCT.

“There is not much debate that you get longer progression-free survival with the more intensive approach. The question is, does progression-free survival matter in mantle cell lymphoma? I argue that it does because relapse in patients with mantle cell lymphoma is no picnic. What you can expect in patients with relapsed or refractory mantle cell lymphoma is a progression-free survival of about 1-2 years, and an overall survival of about 2-3 years,” said Dr. Fenske, head of the section of bone marrow transplant and hematologic malignancies at the Medical College of Wisconsin in Milwaukee.

As an example of the poor prognosis of relapsed or refractory mantle cell lymphoma patients Dr. Fenske cited a review he coauthored of 97 patients treated with ibrutinib (Imbruvica. Their median duration of response was 17 months and median progression-free survival was 15 months. Once ibrutinib treatment failure occurred their median overall survival was less than 3 months. (Hematol Oncol. 2017 Jan 8.doi:10.1002/hon.2380).

“It’s easy to get carried away” when patients temporarily respond to a drug like ibrutinib or other new agents with a degree of efficacy for lymphomas, Dr. Fenske said, but these transient responses “don’t solve the problem. The patient is headed for trouble,” usually within a couple of years.

“I would argue that, especially for younger patients, the goal is to try to achieve the longest first remission, and that means an ASCT.” Dr. Fenske admitted that this strategy won’t work for very-high-risk patients, but for these patients no good treatment options currently exist.

He also stressed that research is just beginning to explore using measurement of negative minimal residual disease to identify patients with the best outcomes following initial induction treatment. It is possible that patients with undetectable minimal residual disease can avoid immediate ASCT and instead receive maintenance therapy, a hypothesis slated for testing in a randomized trial, he said.

Dr. Martin has been a consultant to Celgene, Gilead, Janssen, Novartis, Pharmacyclics, and Verastem. Dr. Fenske has been a consultant to Abbvie, Celgene, Pharmacyclics, Sanofi, and Seattle Genetics.

mzoler@frontlinemedcom.com
On Twitter @mitchelzoler

This article was updated May 30, 2017 .

Newly diagnosed mantle cell lymphoma is ‘one of the hardest consultations’