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