NEW ORLEANSAmong patients with low-grade non-Hodgkins
lymphoma (NHL), combining CHOP (cyclophosphamide, doxorubicin,
vincristine, and prednisone) chemotherapy with rituximab (Rituxan)
adds therapeutic benefit without causing significant additional
toxicity. Rituximab is a human/murine monoclonal antibody that
targets the CD20 antigen on B cells.
We already know that CHOP chemotherapy has activity in
low-grade lymphomas, just as we know that rituximab has activity as
well. What we didnt know was whether we could safely and
effectively combine these two, chemotherapy with immunotherapy,
said Myron S. Czuczman, MD, assistant professor of medicine and head
of the lymphoma service, Roswell Park Cancer Institute, Buffalo, NY.
Dr. Czuczman presented the study results at the 41st Annual Meeting
of the American Society of Hematology.
The study included 40 patients with low-grade follicular NHL, 31 of
whom were treatment naïve. Among the 21 male and 19 female
participants (median age, 48 years), 83% had stage III or IV disease.
CHOP was administered at standard doses over 3 weeks for six cycles
along with six infusions of rituximab (375 mg/m²/dose). Two
doses of rituximab were given both at the beginning and end of
therapy, as well as single doses before the third and fifth cycles of
All of the 38 patients who actually received treatment responded,
with investigators recording complete responses (CR) in 58% of
patients and partial responses (PR) in 42%. Among the 35 patients who
completed all therapy, the overall response rate was also 100% (63%
CR, 37% PR).
The majority of adverse events were mostly grade 1 or 2, with 17% of
overall adverse events reported as grade 3 or 4. They consisted
primarily of hematologic or infectious toxicities felt to be
associated with CHOP chemotherapy.
While cautioning that the current trial was not prospectively
randomized, Dr. Czuczman pointed to some particularly encouraging
findings. We know from many other studies looking at CHOP
chemotherapy that time to progression is usually within about 2
years. Among these patients who received CHOP plus rituximab, we are
now going out to 47.2 months, and more than half of these patients
are still in remission, he said.
Dr. Czuczman noted that some critics might attribute the high success
rate to the fact that 31 of the 40 patients were treatment naïve.
I would say that, perhaps, if these patients continue
progression-free, maybe we should rethink the way we treat patients
with follicular lymphoma, he said.
He noted that this is an incurable illness, and we want the
best possible response. Instead of giving small amounts of drugs and
allowing patients to develop chemotherapy-resistant cells, maybe we
should be using our best arsenal up front, especially since we are
not getting additional toxicity.
In another ASH presentation based on the same study, Antonio J.
Grillo-López, MD, chief medical officer, IDEC Pharmaceuticals
Corporation, San Diego, noted that among the 38 responders, there was
an initial rapid decline in mean SPD (sum of the products of the
perpendicular diameters) of all measurable lesions, with a slower SPD
decline continuing for 10 or more months. That phenomenon, he said,
has been observed previously in rituximab monotherapy and in
combination with CHOP.
Progressive decreases in tumor size can be seen for as long as 16
months, and responses can be achieved, he emphasized, as late as 10
months after treatment. For the usual chemotherapy regimen, you
would see a rapid drop in SPD and then a stabilization rather than a
continued fall, Dr. Grillo-López pointed out in an interview.
The important message, he said, is that if you treat a patient
with the antibody and achieve stable disease (asymptomatic with some
tumor shrinkage), you need to resist the temptation to go right away
to some salvage chemotherapy regimen, because some patients do become
responders later on.