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SAN FRANCISCO—Patients with HIV-related lymphoma (HRL) should not be excluded from clinical trials of autologous stem cell transplant (ASCT) due to their HIV status, new research suggests.
Investigators found no significant difference in rates of treatment failure, disease progression, or survival between transplant-treated historical controls who had lymphoma but not HIV and patients with HRL who received the modified BEAM regimen followed by ASCT on a phase 2 trial.
This suggests patients with chemotherapy-sensitive, relapsed/refractory HRL can be treated successfully with the modified BEAM regimen, said study investigator Joseph Alvarnas, MD, of City of Hope National Medical Center in Duarte, California.
“Patients with treatment-responsive HIV infection and HIV-related lymphoma should be considered candidates for autologous transplant if they meet standard transplant criteria,” he added. “And we would argue that exclusion from clinical trials on the basis of HIV infection alone is no longer justified.”
Dr Alvarnas presented this viewpoint and the research to support it at the 2014 ASH Annual Meeting as abstract 674.
The trial enrolled 43 patients with treatable HIV-1 infection, adequate organ function, and aggressive lymphoma. Three patients were excluded because they could not undergo transplant due to lymphoma progression.
Of the 40 remaining patients, 5 were female, and their median age was 46.9 years (range, 22.5-62.2). They had diffuse large B-cell lymphoma (n=16), plasmablastic lymphoma (n=2), Burkitt/Burkitt-like lymphoma (n=7), and Hodgkin lymphoma (n=15).
The pre-ASCT HIV viral load was undetectable in 31 patients. In the patients with detectable HIV, the median viral load pre-ASCT was 84 copies/μL (range, 50-17,455). The median CD4 count was 250.5/µL (range, 39-797).
Before transplant, 30 patients (75%) were in complete remission, 8 (20%) were in partial remission, and 2 (5%) had relapsed/progressive disease.
The patients underwent ASCT after conditioning with the modified BEAM regimen—carmustine at 300 mg/m2 (day -6), etoposide at 100 mg/m2 twice daily (days -5 to -2), cytarabine at 100 mg/m2 (days -5 to -2), and melphalan at 140 mg/m2 (day -1).
Combination antiretroviral therapy (cART) was held during the preparative regimen and resumed after the resolution of gastrointestinal toxicity. The investigators switched efavirenz to an alternative agent 2 or more weeks prior to the planned interruption of cART, as the drug has a long half-life. And AZT was prohibited due to its myelosuppressive effects.
The median follow-up was 24 months. At 100 days post-transplant, the investigators assessed 39 patients for response. One patient was not evaluable due to early death.
Thirty-six of the patients (92.3%) were in complete remission, 1 (2.6%) was in partial remission, and 2 (5.1%) had relapsed or progressive disease.
Fifteen patients reported grade 3 or higher toxicities within a year of transplant. Of the 13 unexpected grade 3-5 adverse events (reported in 9 patients), 5 were infection/sepsis, 1 was acute appendicitis, 1 was acute coronary syndrome, 2 were deep vein thromboses, 2 were gastrointestinal toxicities, and 2 were metabolic abnormalities.
Seventeen patients reported at least 1 infectious episode, 42 events in total, 9 of which were severe. Fourteen patients required readmission to the hospital after transplant.
Within a year of transplant, 5 patients had died—3 from recurrent/persistent disease, 1 due to a fungal infection, and 1 from cardiac arrest. Two additional patients died after the 1-year mark—1 of recurrent/persistent disease and 1 of heart failure.
At 12 months, the rate of overall survival was 86.6%, progression-free survival was 82.3%, progression was 12.5%, and non-relapse mortality was 5.2%.
“In order to place this within context, we had the opportunity to compare our patient experience with 151 matched controls [without HIV] from CIBMTR,” Dr Alvarnas said. “Ninety-three percent of these patients were actually transplanted within 2 years so that they were the time-concordant group, and they were matched for performance score, disease, and disease stage.”
The investigators found no significant difference between their patient group and the HIV-free controls with regard to overall mortality (P=0.56), treatment failure (P=0.10), progression (P=0.06), and treatment-related mortality (P=0.97).
Likewise, there was no significant difference in overall survival between the HRL patients and controls—86.6% and 87.7%, respectively (P=0.56). And the same was true of progression-free survival—82.3% and 69.5%, respectively (P=0.10).