Topics Alert

Pushing Revlimid

Date: July 22, 2024

I have received queries about Revlimid from several CLL patients, so it is perhaps time to do a little risk/reward evaluation of this drug. While Revlimid seems to be of value in multiple myeloma, I am not too sure of its role in CLL. Below is the report of Revlimid in CLL, by Celgene Corporation, the manufacturer. Presumably this is the best “spin” the company could put on the results of their clinical trial with CLL patients.

Toxicity: Out of 32 patients enrolled in the trial and all of whom were available for toxicity evaluation, the following are reported:

• Two patients withdrew their consent (presumably because they were less than happy with the therapy);
• Five patients received less than the planned amount of therapy and discontinued due to unacceptable toxicity;
• Three patients had the disease progress while on Revlimid and had to switch of Rituxan therapy;
• The classic thalidomide “flare reaction” (swelling of lymph nodes, pain and rash) was seen in almost all patients;
• Tumor lysis syndrome was seen in 2 patients (TLS can be potentially life threatening, may do long term organ damage);
• Grade 3-4 hematological toxicity was seen in 7 patients. (Grade 3 toxicity is serious business, grade 4 is as high as it gets.)
• Febrile neutropenia was seen in 3 patients. (You are advised to get to the emergency room immediately, if you are in this situation).

The company called this “clinically manageable” toxicity profile. Wow, these are brave researchers. I am clearly cut from weaker stuff — I would have said ‘uncle’ in double quick time if threatened with this list of adverse effects. Patients (and patient advocates) are such a whiny, wimpy lot…

Response: Only 19 patients out of the 32 were available for response evaluation. Of these 19 patients, the following responses were seen:

• Sixteen of the 19 patients had a roughly 2/3 reduction in their peripheral blood counts. This is not all that hard to do - a couple of weeks of low dose chlorambucil can reduce peripheral blood counts. Most CLL drugs can do this much, reducing blood counts is easy. The heavy lifting is taking care of bulky lymph nodes and bone marrow infiltration.
• Only 3 patients out of 19 achieved CR. That is a CR rate of less than 16%.
• Ten patients achieved partial response, PR. That is about 53% PR rate.
• Another 3 patients (16%) achieved “Stable disease”, whatever that means.
• Doing the math, all this suggests another 3 patients (16%) had the CLL get worse on them while they were in therapy.

Even for a cohort of previously treated CLL patients recruited for this trial, these results are not worth writing home about, not when one looks at the pretty heavy duty adverse effects encountered. For a very rough comparison, 4 out of 21 previously treated fludarabine refractory patients who got HuMax-CD20 as single agent got CR responses (19%), with a whole lot less toxicity risk. And since we are not prone to grade inflation on our website, we called that “the half-full glass”. Here is the link to the HuMax article HuMax-CD20 Clinical Trial Results. I think on that yardstick the Revlimid results will be judged to be a glass a lot less than half-full. This is one drug I would not be recommending to my hypothetical friend “Harvey”.

Incidentally, only time will tell how lasting these Revlimid responses will be. As for the adverse effects, prior history with its parent compound (thalidomide) suggests we ought to think twice about longer term adverse effects that are not reported in this hot-of-the-presses and no doubt best-foot-forward report by the company. In multiple myeloma trials there is a suggestion that there may be neurological damage in some of the patients — peripheral neuropathy has been reported. Damn, it is one pesky “clinically manageable” adverse effect after the other.

Bottom line, I suggest a careful consideration of the risks versus rewards of this particular compound before anyone signs on the dotted line. This is by no means a free lunch, or even a low risk option.

As additional reading material, we reviewed Revlimid’s parent compound thalidomide in a recent Topics Alert, #154.

Be well,

Chaya
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Press Release

Celgene Corporation (Nasdaq: CELG - News) announced that clinical data from a REVLIMID study in Chronic Lymphocytic Leukemia (CLL) were reported at an oral presentation during the 47th American Society of Hematology (ASH) Meeting in Atlanta, GA on Monday, December 12, 2024.

The study reported that sixteen out of nineteen evaluable patients achieved stable disease or better after treatment with lenalidomide, and experienced a median decrease of 61 percent in absolute lymphocyte count (ALC), a measure of tumor burden. Five patients achieved complete response (CR), two of the five patients achieving molecular (CR). Ten patients achieved partial response (PR) and three patients achieved stable disease (SD). Progressive disease (PD) was reported in three patients.

About the Trial

The lead author of this presentation was Asher Chanan-Khan, M.D., Roswell Park Cancer Institute, Buffalo, New York.

Dr. Chanan-Khan reported thirty-two relapsed or refractory CLL patients, median age of 64 years (age range: 47-75) were enrolled in the trial with all patients available for toxicity and nineteen patients available for response evaluation. REVLIMID was given at 25mg orally every day for 21 days followed by 7 days of rest on a 28-day cycle. Absolute lymphocyte count (ALC) at days 0, 7 and 30 were taken to determine direct anti-CLL effect of lenalidomide (REVLIMID). Response was assessed at day 30, and then monthly using the National Cancer Institute-Working Group criteria. CLL patients with SD or better response continued on therapy until CR and those with PD then received Rituximab at (375mg/m2) added to lenalidomide (REVLIMID). Sixteen out of nineteen patients responded with a median decrease of 61% in absolute lymphocyte count (ALC), (range: 55-70%). Three patients achieved CR with 2 achieving a molecular CR, ten patients achieved PR and three patients achieved SD. Four patients on treatment are too early for response assessment. Two patients withdrew consent and five patients received less than two months of therapy due to toxicity. Progressive disease has been observed in three patients, and therefore have received Rituximab. All three patients have responded to the combination therapy.

Toxicity profile was clinically manageable. The most common side effect was a flare reaction (tender swelling of lymph nodes and/or rash) in almost all patients, and tumor lysis syndrome was noted in two patients. Grade 3 /4 toxicities included hematologic toxicities in seven patients and febrile neutropenia in three patients. While the longest follow up is 12 months, further follow-up and analysis will ascertain the durability of these responses and establish the role of lenalidomide (REVLIMID) as a potential treatment of patients with CLL.

"Based on the study results we are moving ahead with clinical studies and preparing regulatory strategies for lenalidomide (REVLIMID) in CLL," said Sol J. Barer, Ph.D., President and Chief Operating Officer of Celgene Corporation.

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