Adding rituximab to chemotherapy regimens improves outcomes for AIDS-related lymphomas

The addition of rituximab to chemotherapy regimens for the treatment of AIDS-related lymphomas improves both overall survival and progression-free survival, German investigators report in the online edition of AIDS.

Therapy with rituximab appeared to be safe, and no deaths were associated with its use.

“Rituximab was beneficial for AIDS-related lymphoma even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections,” comment the authors.

Cases of AIDS-related lymphoma have fallen significantly since the introduction of effective antiretroviral therapy. There has also been a marked improvement in the outcomes of individuals diagnosed with the malignancy.

Nevertheless, these cancers are an important cause of the excess mortality that still occurs in HIV-positive patients. Their treatment is controversial and there is some uncertainty about the benefits of adding rituximab – a monoclonal CD20 antibody – to traditional CHOP-based (cyclophosphamide, doxorubicin, vincristine and prednisone ) chemotherapy regimens.

Investigators from Germany therefore analysed the outcomes of patients diagnosed with AIDS-related lymphomas between 2005 and 2008 according to their treatment regimen and the use of the rituximab.

A total of 156 individuals who received care at 25 clinics across Germany were included in the study. These patients had a median age of 45 years, and almost all (92%) were men.

Many of the patients had severe immunosuppression at the time of cancer diagnosis.

Median CD4 cell count was 205 cells/mm³, and a quarter of patients had a CD4 cell below 100 cells/mm³. In two-thirds of patients, the lymphoma was the first AIDS diagnosis. Over half the patients had never taken antiretroviral therapy.

“Thus, a relevant proportion of our patients were late presenters”, emphasise the authors.

Forty-seven per cent of patients were treated with rituximab in addition to their CHOP-based regimen. A median of four rituximab doses were administered.

By the end of 2008, a total of 61 patients (37%) had died after a median of 15 months of follow-up.

After taking into account potentially confounding factors, the investigators found a strong relationship between treatment with rituximab and the chances of survival.

Compared to individuals treated with a traditional CHOP-based regimen, the chances of overall survival were significantly better for patients who also received rituximab (OR = 0.43; 95% CI, 0.21-0.89). The addition of the drug also improved progression-free survival (OR = 0.44; 95% CI, 0.23-0.84).

Expression of CD20 was also a significant predictor of survival (OR = 0.24; 95% CI, 0.12-0.47). A subgroup analysis was therefore performed involving patients with this immune characteristic. This once again showed that rituximab improved both overall survival (OR = 0.42; 95% CI, 0.20-0.87) and progression-free survival (OR = 0.44; 95% CI, 0.23-0.84).

A CD4 cell count above 100 cells/mm³ also predicted the chances of survival in both sets of analysis.

The investigators then turned their attention to the safety of rituximab therapy. As has been noted, 61 patients died. In two-thirds of cases, the cause of death was lymphoma. Infections caused a fifth of deaths, and 11% were due to other causes such as heart attack, liver failure and suicide.

All deaths due to fatal infections were considered to be treatment-related. Three of these twelve deaths involved patients treated with rituximab. Immune suppression appeared to be the main cause of these deaths. Regardless of treatment regimen, the median CD4 cell count at the time of death was in the region of 100 cells/mm³.

“We did not observe an increased risk of fatal infections due to use of rituximab,” write the authors. “However, the patients who died from treatment-associated infections had lower CD4 T-cells than the entire group. These findings emphasise the need for prospective trials evaluating the benefits of intensified supportive care.”

They conclude, “the use of rituximab improved overall and progression free-survival.  This effect was seen even in the setting of severe immune deficiency and without an increased risk of fatal infections.”

Noting the substantial mortality rate, the investigators call “for further clinical research in AIDS related lymphomas.”

Wyen C et al. Treatment of AIDS-related lymphomas (ARL): rituximab is beneficial even in severely immunosuppressed patients. AIDS 25, online edition. DOI: 10.1097/QAD.0b013e32834f30fa, 2011 (click here for the free abstract).