ASH 2015: Risk profile key in transplant decisions in non-Hodgkin lymphoma

by Thomas R. Collins: There could be a role for consolidation autologous stem cell transplantation for patients with diffuse, aggressive non-Hodgkin lymphomas (NHL) who are at high risk of disease progression, an expert said here at ASH.

“There may be a benefit — (in) progression-free and overall survival — to early transplants for high IPI (International Prognostic Index) disease for both the B- and the T-cell type,” said Dr Patrick Stiff, MD, Director of the Cardinal Bernardin Cancer Center at Loyola Medical University.

But — in a session in which he stressed the increasing complexity in the understanding of the role transplantation in the NHL setting — he stressed that transplantation doesn’t have a place in patients with a low, intermediate, or high-intermediate score on the IPI.

Guidance, he said, is still best pulled from a Memorial Sloan-Kettering study from 2010¹, in which patients with a high IPI or high-intermediate IPI received dose-dense R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy for four cycles then underwent a PET scan. If that was positive, they underwent a biopsy. If the biopsy was positive, then they went to transplant. If it was negative, or they had had a negative PET scan, they were observed after 3 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy.

The results, Dr. Stiff said, were “impressive for both PET-negative and PET-positive disease,” suggesting that the study touched on an appropriate approach for several risk categories.

In relapsed or refractory patients, those who are less responsive to therapy are appropriate for allo-transplantation. But he added that those who are not candidates for allografts should still be considered for clinical trials.

“A degree of responsiveness in salvage is still the main predictor of outcome,” Dr. Stiff said. “And since only 50% of patients who relapse ever make it to transplant, this to me is the low-hanging fruit and we should approve pre-transplant salvage therapy as priority before designing new additional trials.”

In another hard-to-treat group, double-hit or double-protein NHL, he emphasized how time is of the essence: median survival time in double-hit patients is just 8 months.²

Either R-EPOCH (rituximab, etoposide, prednisone vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride) or R-hyper-CVAD (rituximab, cyclophosphamide, vincristin sulfate, doxorubicin hydrochloride and dexamethasone) are “fair game” in these diseases if they’re identified quickly, Dr. Stiff said.

But even get a response — even without a complete response — should be enough to move a patient on to auto-transplantation.

“These patients die quickly,” Dr. Stiff said. “So until phase III data proves that transplant does not add to the outcome, or a better method is found to determine who will relapse early, an early transplant is considered still appropriate for these patients in which transplant is given generally before months more of therapy for responding double-hit (or) double-protein patients.”

Asked how soon a patient should move to transplant if they respond quickly, Dr. Stiff said, “Quick—I would say if you’ve waited more than 4 months you’re probably too long.”

He said that, overall, the question of transplantation on NHL has been complicated by the discovery of much more heterogeneity than the field knew about even 5 years ago. Plus, the amount of types of therapies has mushroomed.

“This has further cut down the sample sizes for clinical trials and for patient populations,” he said, “and makes it more difficult to describe whether a patient should or shouldn’t have a transplant.”

 

References

1.  Moskowitz C, Schoder H, Teruva-Feldstein J, et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol. 2010 Apr 10;28(11):1896-903.

2.  Petrick A, Gandhi M, Jovanovic B, et al. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood. 2014 Oct 9;124(15):2354-61.