This month, Mitchell Smith, MD, PhD, discusses the role of transplant in gamma-delta T-cell lymphoma.
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I have a 44-year-old patient with multiple subcutaneous nodules initially felt to be a granulomatous process/panniculitis. A biopsy has now demonstrated a primary cutaneous gamma-delta T-cell lymphoma. The staging/pretreatment evaluation is ongoing, but he is having night sweats with new lesions appearing. It appears the general recommendation is for multi-agent peripheral T-cell lymphoma regimens such as cyclophosphamide, doxorubicin, etoposide, vincristine, and prednisone (CHOEP). Would there be a role for up-front transplant as well?
As cutaneous gamma-delta T-cell lymphoma can be a challenging diagnosis, it is important to ensure the pathology has been reviewed by an expert in cutaneous lymphoma. Assuming that is the case, there are minimal data to guide us in choosing the optimal therapy.
In a few of these cases, the disease behaves more indolently, but that does not appear to be the situation in this patient, given the night sweats and the rapid development of new lesions. So, therapy is warranted. For initial therapy, given the rarity of cutaneous gamma-delta T-cell lymphoma, we extrapolate from peripheral T-cell lymphoma (PTCL) data, which are still limited.
CHOEP is a reasonable selection. Retrospective analyses by the German High-Grade Lymphoma Study Group suggest this treatment can lead to prolonged progression-free survival, but not improved overall survival, in patients with PTCL under age 60 years. Whether CHOEP is superior to CHOP, or even whether C-etoposide-OP (CEOP) is adequate, has not been formally tested. Based on the ECHELON-2 trial, one would consider CH-brentuximab vedotin (BV)-P, which was superior to CHOP in CD30-positive PTCL, if this patient’s lymphoma is CD30 positive. While other cutaneous T-cell lymphomas can respond to BV even if CD30-negative by immunohistochemistry, there are no supporting data for this approach in this subtype.1
Some groups advocate first-line platinum-based regimens, usually combined with gemcitabine, for PTCL, given the poor outcomes with CHOP-like therapy. A recent parallel-group phase II trial, however, suggests that gemcitabine, cisplatin, and methylprednisolone (GEM-P) was not superior to CHOP.2 Outcomes in a prior SWOG phase II study (S0350) of platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) as initial therapy for PTCL were considered not promising.3 If the patient attains remission, the general recommendation would be to proceed with allogeneic hematopoietic cell transplantation (alloHCT). Again, this is based on essentially anecdotal data, but probably represents the best (only?) chance for durable remission. While consolidation of PTCL in first remission with high-dose chemotherapy/autologous stem cell support is generally recommended when feasible, no randomized data exist to support this. In this particular subtype in which standard chemotherapy is not very effective, my preference would be for alloHCT.
If the patient does not attain durable remission, later-line therapeutic options are limited, again extrapolated from PTCL. At that point, clinical trial options should be explored.
So, my recommendation would be to confirm this rare diagnosis, induce with CH-BV-P if CD30-positive, or CHO(E)P if not, and consolidate remission with alloHCT.
- Horwitz S, O’Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393:229-40.
- Gleeson M, Peckitt C, To Y, et al. CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial. Lancet Haematol. 2018;5:e190-e200.
- Mahadevan D, Unger JM, Spier CM, et al. Phase II trial of cisplatin plus etoposide plus gemcitabine plus solumedrol (PEGS) in peripheral T-cell non-Hodgkin lymphoma (SWOG S0350). Cancer. 2013;119:371-9.
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NEXT MONTH'S CLINICAL DILEMMA
In Norway, I follow a fit 72-year-old patient who was diagnosed with IgG-lambda myeloma in the summer of 2016. At that time, he had anemia, osteolytic lesions, and renal dysfunction. He was treated with lenalidomide plus dexamethasone, but this gave him even more renal dysfunction with no response. After that, he was treated with daratumumab, bortezomib, and dexamethasone (we don’t have daratumumab plus pomalidomide and dexamethasone), but there was no effect. Pomalidomide plus low-dose dexamethasone was effective, as was daratumumab plus pomalidomide and dexamethasone. Now he has a bulky plasmacytoma in his thorax, which was treated with radiation but with bad results.
He is fit, but he is 72 years old and has a very active disease. What would you advise? Back to some traditional chemotherapy to see whether he tolerates it? Melphalan, but in combination with what?
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