The MDACC lot have published the results of a phase 2 trial of FC with Ofatumumab in 61 previously untreated CLL patients. The question we all want to know is whether O-FC is likely to be an improvement on FCR.
The problem with a phase 2 study is that there is no comparison that is valid. All you can do is look at other phase 2 studies and make a rough judgement.
So what is the competition like? The CALGB 9712 trial reported at CR rate of 47% and an OR rate of 90% for FR. The MDACC FCR response rate was 72% CR and 95% OR. The Spanish FCM-R rates were 82% CR and 93% OR. But the German CLL8 study reported a more realistic 44% CR rate and 95% OR, All these studies were in relatively young and fit patients.
However, the O-FC study was a bit more stringent in some respects, though not all. The patients were still young with a median age of 56, but they included 13% with a del 17p and 16% with del 11q. 64% had a Beta-2M level greater than 3.5. 47% were unmutated and 20% had a raised CD38. Of particular note was the OR of 63% and CR rate of 13% in del 17p patients.
The overall incidence of toxicity and failure to complete treatment was similar to the MDACC experience with FCR.
The FC was given in standard doses but the O was given as either 500 or 1000 mg (not per sq m). The OR rate was 77% and 73% for the two doses respectively (ie not statistically different) but the CR rate was 50% for the higher dose and 32% for the lower (not statistically different, though because of small numbers). By univariate analysis the factors determining response were completion of sufficient courses of treatment and the Beta-2M level.
What can we say then, is O-FC as good as FCR? This small study is unable to say more than it might be. We shall have to await head to head comparisons.
1 comment:
Of course the real problem with FCR and O-FC is the probability of further mutations in the CLL cells leading to an increased risk of Richter's Transformation and myelodyplastic syndrome (MDS).
Both are terrible killers, killing one fast.
In this era of kinase inhibitors (CAL-101 and others), it is my opinion that FCR should be reserved for the truly ill with no other options.
Because it is a fact that once you relapse from FCR (and you will), there are few options left.
Why would any CLLer take this as a first course treatment? Crazy that anyone (hello, M.D. Anderson!) would recommend FCR as a first line therapy.
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