Conference Coverage

MCL treatment choices depend partly on age


 

EXPERT ANALYSIS FROM MHM 2018

– Treatment for mantle cell lymphoma (MCL) depends at least in part on patient age, with some important differences in those aged 65 years or younger versus those over age 65, according to Kristie A. Blum, MD.

Mantle cell lymphoma histology Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Mantle cell lymphoma

“For the [younger] early-stage patients I’ll think about radiation and maybe observation, although I think [observation] is pretty uncommon,” Dr. Blum, acting hematology and medical oncology professor at Emory University in Atlanta, said at the American Society of Hematology Meeting on Hematologic Malignancies.

For advanced-stage patients, a number of options, including observation, can be considered, she said.

Observation

Observation is acceptable in highly selected advanced stage cases. In a 2009 study of 97 mantle cell patients, 31 were observed for more than 3 months before treatment was initiated (median time to treatment, 12 months), and at median follow-up of 55 months, overall survival (OS) was significantly better in the observation group (not reached vs. 64 months in treated patients), she said (J Clin Oncol. 2009 Mar 10;27[8]:1209-13).

Observed patients had better performance status and lower-risk standard International Prognostic Index scores, compared with treated patients, and the authors concluded that a “watch-and-wait” approach is acceptable in select patients.

“In addition, if you looked at their overall survival from the time of first treatment, there was no difference in the groups, suggesting you really weren’t hurting people by delaying their therapy,” Dr. Blum said.

In a more recent series of 440 favorable-risk MCL patients, 17% were observed for at least 3 months (median time to treatment, 35 months), 80% were observed for at least 12 months, and 13% were observed for 5 years.

Again, median OS was better for observed patients than for those treated initially, at 72 months vs. 52.5 months (Ann Oncol. 2017;28[10]:2489-95).

“So I do think there is a subset of patients that can safely be observed with mantle cell [lymphoma],” she said.

Transplant-based approaches

Transplant-based approaches in younger patients with advanced disease include the Nordic regimen plus autologous stem cell transplant (ASCT), R-CHOP/R-DHAP plus ASCT, and R-bendamustine/R-cytarabine – all with post-ASCT maintenance rituximab, Dr. Blum said.

Cytarabine-containing induction was established as the pretransplant standard of care by the 474-patient MCL Younger trial, which demonstrated significantly prolonged time to treatment failure (9.1 vs. 3.9 years), with alternating pretransplant R-CHOP/R-DHAP versus R-CHOP for six cycles, though this was associated with increased toxicity. (Lancet. 2016 Aug 6;388[10044]:565-75).

For example, grade 3-4 thrombocytopenia occurred in 73% vs. 9% of patients, she noted.

The Nordic MCL2 trial showed that an intensive regimen involving alternating Maxi-CHOP and AraC followed by transplant results in median OS of about 12 years and PFS of about 8 years.

“I do want to highlight, though, that again, the high-risk patients don’t do very well,” she said, noting that median PFS even with this intensive approach was only 2.5 years in those at high risk based on MCL International Prognostic Index (MIPI) score, compared with 12.7 years for patients with a low-risk MIPI score.

Newer induction regimens also show some promise and appear feasible in younger patients based on early data, she said, noting that the SWOG S1106 trial comparing R-bendamustine and R-HyperCVAD showed a minimal residual disease (MRD) negativity rate of 78% in the R-bendamustine group. Another study evaluating R-bendamustine followed by AraC showed a 96% complete remission and PFS at 13 months of 96%, with MRD-negativity of 93% (Br J Haematol. 2016 Apr;173[1]:89-95).


Transplant also is an option in advanced stage patients aged 66-70 years who are fit and willing, Dr. Blum said.

“I spend a long time talking to these patients about whether they want a transplant or not,” she said.

For induction in those patients who choose transplant, Dr. Blum said she prefers bendamustine-based regimens, “because these have been published in patients up to the age of 70.”

Transplant timing is usually at the first complete remission.

Data show that 5-year OS after such early ASCT in patients with no more than two prior lines of chemotherapy is about 60%, compared with about 44% with late ASCT. For reduced intensity conditioning allogeneic stem cell transplant in that study, the 5-year OS was 62% for early transplant and 31% for late transplant (J Clin Oncol. 2014 Feb 1;32[4]:273-81).

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