This month Ann S. LaCasce, MD, MMSc, discusses whether a patient with high-risk DLBCL should receive rituximab maintenance after R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) or autologous transplantation.
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I am caring for a 67-year-old man with stage 4B diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma. He presented with breathlessness and weight loss for 1 month. His malignant cells in the bone marrow were BCL2 positive on a fluorescence in situ hybridization (FISH) test, but negative for c-Myc and BCL6. A PET/CT scan showed diffuse marrow uptake in the axial and appendicular skeleton, increased uptake in his liver and spleen, and extensive hypermetabolic lymph nodes in his abdomen above and below the diaphragm. His lactic acid dehydrogenase (LDH) level at the time of diagnosis was above 700 U/L and his beta-2 microglobulin level is 3.5 times the upper limit of normal. His creatinine level was normal, alkaline phosphatase (ALP) level was 1,268 U/L, and his alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were about 175 U/L. He had severe lactic acidosis and his uric acid level was 2 times the upper limit of normal.
After 3 cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone), a PET/CT scan shows resolution of all uptake with a score of 1 on the Deauville scale. His LDH remains normal but his beta-2 microglobulin level is still slightly elevated. The patient is clinically well and fit. He received 2 cycles of intrathecal chemotherapy, and there is no evidence of CNS involvement by the lymphoma. He was recently given high-dose methotrexate and cycle 4 of RCHOP therapy. We are planning to administer 6 cycles of RCHOP, of which 2 cycles will be with methotrexate. I would appreciate advice on management going forward. Is rituximab maintenance preferable? Is there any role for autologous transplant?
I fully agree with the plan for 6 cycles of R-CHOP chemotherapy. I share the concern that a high-risk patient with an International Prognostic Index (IPI) score of 5 may do poorly, but there is no evidence that more intensified regimens are associated with better outcomes (see recent Alliance study comparing R-CHOP vs. R- EPOCH).1 In addition, given the patient’s high Central Nervous System IPI, the use of systemic methotrexate prophylaxis is warranted.
With regard to maintenance rituximab, a large, randomized study did not demonstrate any benefit of maintenance in patients with large cell lymphoma receiving R-CHOP as initial therapy.2 In addition, consolidation with autologous transplantation in first remission has been tested in a number of trials, and there is not clear evidence of benefit for this strategy even in higher-risk patients. I don’t think the beta-2 microglobulin level is informative in the setting of a negative PET and can be elevated for reasons other than persistent lymphoma.
If the patient develops recurrent disease, particularly if it occurs soon after the completion of R-CHOP/methotrexate, I would suggest early evaluation for CAR-T cell therapy, as he has a high risk of being refractory to salvage chemotherapy.
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NEXT MONTH'S CLINICAL DILEMMA
I am an oncologist requesting advice about a 71-year-old man with recurrent coronary artery closure. He had a stent placed in April 2019, which occluded, and he underwent coronary artery bypass grafting (CABG) 4 months later. In April 2020, a grafted vessel occluded. Since April 2019 he has received clopidogrel, ticagrelor, and prasugrel at different times. Now he is on aspirin only. His cardiologist did a hypercoagulability work-up and found a mildly decreased protein S activity level of 57%. I conducted the test a few days later and found that his protein S activity level was 70%. I am planning to repeat the test in 4 weeks. The patient is due to undergo repeat CABG soon. Is there any role for warfarin?
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