The THRIL (thalidomide [T], rituximab [R], and lenalidomide [L]) regimen for chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma: daily alternating IMiDs and rituximab maintenance

[Guest guest]

Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting

Edition).

Vol 26, No 15S (May 20 Supplement), 2008: 7079

The THRIL (thalidomide [T], rituximab [R], and lenalidomide [L]) regimen for

chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell

lymphoma: daily alternating IMiDs and rituximab maintenance

M. , P. , J. Ruan, R. Niesvizky, J. P. Leonard, R. Elstrom and R.

R. Furman

Weill Cornell Medical College, New York, NY

7079

Background: The immunomodulatory drugs (IMiDs) thalidomide (T) and lenalidomide

(L) have been reported to be effective agents in chronic lymphocytic leukemia

(CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Marrow

toxicity often limits the use of L when used as part of the 21 day on, 7 day off

schedule, whereas neurologic toxicity prevents the long term use of T. In

contrast, L produces minimal risk of neurologic toxicity and T results in no

marrow toxicity. Preliminary data suggest that T and L may not be cross

resistant and may possibly be synergistic in combination. Alternating T with L

on a daily basis may ameliorate neurologic and marrow toxicities of each by

reducing the total dose of either drug and result in an improved response.

Methods: 11 pts with CLL/SLL and 3 with MCL, most with heavily pre-treated

disease, were treated with a regimen of rituximab 375 mg/m2 weekly x 4 every 6

months, T 50 mg alternating with L 10 mg daily on a continuous basis, and 162 mg

aspirin daily. Results: Of the 14 pts, 2 CLL pts achieved a CR by 4-color flow

and 2 MCL pts by bone marrow/CT criteria. There were 3 PRs (2 CLL and 1 MCL), 3

SDs (all CLL), and four non- responders (all CLL). Median follow-up is 5 months

(range 2-21, mean 6). There have been 4 instances of tumor flare, all in CLL

pts, treated briefly with steroids and which heralded a response. Rash related

to T or L occurred in 4 pts, prompting withdrawal of therapy in 2 pts, both of

whom were responding. 7 pts are off treatment because of lack of response (4

pts), progression of disease after responding (1 pt), or rash (2 pts). No pts

experienced significant neurologic toxicity or suffered thromboemoblic events,

and in only two instances was L held briefly for cytopenias. Conclusions: These

data suggest daily alternating T+L as part of the THRIL regimen may be an

effective method of reducing toxicity while achieving responses in patients by

enabling longer, continuous use of IMID therapy. Whether enhanced responsiveness

results from the combined sequential use of T and L requires further

investigation. This approach may also merit exploration in other IMiD responsive

diseases, particularly myeloma and myelodysplasia.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting