Results from the BMT CTN 0803/AIDS Malignancy Consortium 0071 study debunk the myth that HIV-positive patients with lymphoma are unsuitable for autologous hematopoietic cell transplantation (AHCT), according to a report published in Blood. Overall and progression-free survival rates were higher than 80 percent among these patients, and were comparable to outcomes in patients with lymphoma who are not infected with HIV.
Previous research has been limited because patients are largely treated at centers with HIV-specific expertise, and HIV infection is often an exclusion criterion for transplant-related clinical trials. In this phase II, multi-center, prospective trial, Joseph C. Alvarnas, MD, from the City of Hope National Medical Center in Duarte, California, and colleagues, evaluated the safety and effectiveness of AHCT in 40 patients with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) who had a treatment-responsive HIV infection. Patients were enrolled at 16 transplant centers between April 2010 and March 2013.
Patients (age ≥15 years) with documented HIV infection were included in the study if they had:
- a Karnofsky performance status >70%
- persistent or recurrent diffuse large B-cell immunoblastic, plasmablastic, Burkitt, or Burkitt-like NHL; or classic HL
- received ≤3 prior treatment regimens and ≤2 salvage chemotherapy
- adequate organ function for AHCT
- <10% marrow involvement after the most recent salvage therapy
- not received prior AHCT or allogeneic HCT
- achieved adequate hematopoietic progenitor cell mobilization (>1.5 x 106 CD34+ cells/kg)
The preparative regimen for AHCT consisted of modified BEAM therapy:
- Carmustine 300 mg/m2 taken on the sixth day prior to AHCT
- Etoposide 100 mg/m2 twice daily taken on the fifth through second days prior to AHCT
- Cytarabine 100 mg/m2 twice daily taken on the fifth through second days prior to AHCT
- Melphalan 140 mg/m2 taken one day prior to AHCT
Combination antiretroviral therapy (cART) was held from the time of initiation of the BEAM regimen and resumed at least seven days after completion of the preparative regimen or following recovery from transplant-related gastrointestinal toxicities. All patients received growth factors, transfusions, and antimicrobial supportive care per their treating institution’s standards.
One-year overall survival (OS) was the study’s primary endpoint; secondary endpoints included progression-free survival (PFS), complete remission (CR), and overall response rates (ORR). Patients underwent disease status assessments prior to AHCT, and at 100 days and one year post-AHCT. Hematopoietic recovery was defined as an absolute neutrophil count (ANC) >1,500 µ/L, untransfused hemoglobin >10 gm/dL, and untransfused platelets >100,000/µL.
All 40 patients (median age = 46.9 years; range = 22.5-62.2 years) were followed for a median of 24.8 months (range = 2.8-27.7 months).
One-year OS was 87.3 percent (95% CI 72.1-94.5), and two-year OS was 82 percent (95% CI 65.9-91%). The probability of two-year PFS was 79.8 percent (95% CI 63.7-89.4).
At the time of transplant, 30 patients (75%) were in CR, nine (22.5%) were in PR, and one patient (2.5%) with disseminated HL had progression at a single nodal site immediately prior to transplant after achieving a CR to salvage therapy. At 100 days post-AHCT, 36 patients (92.3%) were in CR, one (2.5%) was in PR, and two (5.1%) had relapsed/progressive disease.
During follow-up, seven patients died – five within one year of transplant, for an estimated risk of one-year transplant-related mortality of 5.1 percent. Three of these five patients died of relapsed/progressive disease, one died of organ failure, and one from fungal infection.
The median time to post-transplant neutrophil recovery was 11 days, with a median time to platelet recovery of 18 days. At 100 days and one-year post-autoHCT, 28.9 percent (n=11/38) and 74.2 percent (n=23/31), respectively, of evaluable patients achieved hematologic recovery.
Fifty-five percent of patients (n=22) experienced at least one infectious event within one year post-AHCT, with a total of 57 infections occurring: 25 due to bacteria, 22 due to viruses, six due to fungal organisms, two due to protozoa, and two caused by other organisms.
Nine patients experienced a total of 13 unexpected grade 3 (n=10) and 4 (n=3) adverse events (AEs) following transplant, including: infection/sepsis (n=5), venous thromboembolism (n=2), esophageal candidiasis (n=1), enteritis (n=1), hyperglycemia (n=1), hypernatremia (n=1), acute appendicitis (n=1), and acute coronary syndrome (n=1).
Sixteen patients required readmission following the initial admission for AHCT, with a total of 34 readmissions; the most common causes for readmission were infection (n=18) and fever (n=6).
“There does not appear to be any long-term loss of CD4+ T cells following AHCT,” Dr. Alvarnas and colleagues noted. “Significant, long-term worsening of T-cell immunity is not a complication of transplant.” Immunologic reconstitution studies demonstrated that immunoglobulin (Ig) levels and CD4+ T cells were recovered by one year post-AHCT. Median IgG, IgA, and IgM levels recovered to 1,090 mg/dL (range = 270.0-2331.0), 123 mg/dL (range = 6-534), and 48.5 mg/dL (range = 24-254), respectively; median CD4+ T-cell count recovered to 280.3/µL (range = 28.8-1148.0).
When the results from the HIV-positive population were compared with a matched population of 151 non-HIV transplant recipients from the Center for International Blood and Marrow Transplant Research database, the outcomes did not differ statistically between the two patient populations. The probability of one-year OS in the control group was 87.7 percent (95% CI 80.9-92.2), and the probability of PFS was 69.5 percent (95% CI 61.1-76.4). And, as seen in TABLE, hazard ratios for mortality and other endpoints were similar.
“Together, these trials validate the concept that controlled HIV-infection should not preclude consideration of AHCT for patients who otherwise meet standard transplant eligibility criteria,” the authors concluded. “Patients with HIV-related lymphoma should also be considered appropriate potential participants for future AHCT clinic trials.”
While these results are encouraging, Dr. Alvarnas and colleagues noted some important HIV-related clinical issues that should govern the care of patients with HIV-related lymphoma, including monitoring any potential drug-drug interactions between anti-HIV therapy and AHCT-related regimens, and carefully deciding when to continue or discontinue anti-HIV therapy to avoid the risk of increasing HIV resistance.
Alvarnas JC, Rademacher JL, Wang Y, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the (BMT CTN) 0803/AIDS malignancy consortium (AMC) 071 trial. Blood. 2016 June 13. [Epub ahead of print]
|TABLE. Comparison of Outcomes of HIV-Infected Patients With Controls|
|Outcome||HIV-Infected Patients (n=40) vs. Controls (n=151)|
|Hazard Ratio||95% CI||p Value|
|Time to platelet recovery||0.88||0.60-1.28||0.49|