Most people are agreed that FCR is the best first line therapy if you are fit enough. CAL-101 and PCI32765 both look promising as disease modifying agents that act a bit like Gleevec for CLL, though the jury is still out on long-term effects. What about second-line in patients who have responded well to FCR?
It seems that repeating FCR in patients who have had a 2-year remission and not suffered major problems with it first time around is probably the right idea. However, few people will be able to get six course in a second time and the older patient and one with co-morbidities might be better advise not to try.
Is there a place for bedamustine plus rituximab as second line in patients declared unfit for a second FCR? An Italian atudy has addressed this issue. They evaluated bendamustine plus or minus rituximab in a group of heavily pretreated patients.
109 patients of median age 66 (39-85) were included. There were 80 males. 20 had B symptoms. Median prior therapies was 3 (1-8). 38% had received previous fludarabine and 39% had had previous rituximab. 62 were resistant to their last treatment. 22 received bendamustine alone and 87 the combination of bendamustine + rituximab. There was no attempt to randomize between them and I can't really see the point of lumping the together. This was the B J Haem. In Leukemia Research we would have been a bit more stringent about how the trial was reported. In fact it wasn't a trial at all, but a retropective look back at how bendamustine had been used in 24 Italian centers. I am afraid I would have rejected the paper for Leukemia Research.
105 patients were evaluable for response. 30 obtained CR, 43 a PR and 32 obtained no response. The CR rate for B+R was 32.5% and only 13.6% for B alone. Responsive patients had a better response (84.8%) than resistant patients (57.6%) (p=0.004). The median duration of response was 13 months.
Only 36% of patients received the intended 6 courses. 7% received 5 courses, 21% 4 courses and 34% 1-3 courses. Four patients were stopped early because of toxicity (1 herpetic encephalitis, 1 relapse of a melanoma, 1 myocardial infarction and 1 grade 4 neutropenia. 16.5% had grade 4 neutropenia and 17.5% thrombocytopenia, 15.5% anemia and 4.5% infection. Three of the 34 deaths were thought to be treatment-related.
What to make of this study? In view of my previous posting, not much. This was not a trial with an independent review panel. Responses were assessed by the patients' individual doctors and bias easily creeps in. The median duration of response was just over a year - not very long. All we can say is that Bendamustine is a drug that has some response in previously treated patients. A year later roughly a third of those treated were dead. I'm not sure what was gained by publishing this report. I am not impressed.