Lenalidomide Shows Some Antitumor Activity in Patients With Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma

Patients with adult T-cell leukemia/lymphoma (ATLL) that is resistant to chemotherapeutic regimens have few treatment options. Following a phase I study determining the maximum-tolerated dose of lenalidomide for patients with ATLL, investigators evaluated the efficacy and safety of 25 mg/day of lenalidomide in the multicenter, single-arm, open-label, phase II ATLL-002 study, which enrolled 26 patients with unfavorable-risk ATLL.

Takashi Ishida, MD, PhD, from the Department of Hematology and Oncology at the Nagoya City University Graduate School of Medical Sciences in Japan, and authors published the results of the study in the Journal of Clinical Oncology.

Though the humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab, was recently approved in Japan (where the ATLL-002 study was conducted) for CCR4-positive ATLL, most patients with ATLL will relapse following therapy, the authors explained. In this study, monotherapy with oral lenalidomide led to an overall response rate of 42 percent (n=11; the study’s primary endpoint), including four complete responses (CRs; 15%) and one unconfirmed CR (CRu; 4%).

“Efficacy [for lenalidomide] also was even seen after treatment with mogamulizumab,” Dr. Ishida told ASH Clinical News. “Since lenalidomide’s mechanism of action is different from that of mogamulizumab, patients who are refractory to mogamulizumab may benefit from lenalidomide treatment. In addition, with lenalidomide being an oral drug, elderly patients and patients with unfavorable performance status can benefit from an easy-to-use oral treatment.”

The ATLL-002 study included patients >20 years old with aggressive ATLL who had received at least one prior therapy but had relapsed (defined as patients who achieved CR from previous therapy and experienced subsequent disease progression) or who had disease recurrence (defined as patients who achieved partial response or stable disease on previous therapy and experienced subsequent disease progression). Patients also had:

  • an Eastern Cooperative Oncology Group performance status of 0-2
  • at least one measurable lesion by computed tomography scan
  • peripheral blood or skin lesions

Patients were excluded if they had:

  • absolute neutrophil count <1,200/μL
  • platelet count <75,000/μL

Twenty-six patients (14 male and 12 female) were enrolled between November 2012 and September 2014. The median patient age was 68.5 years (range = 53-81 years), and patients had received a median of two prior therapies (range = 1-4 therapies).

At data cutoff (November 2014), five patients (19%) remained on treatment, while the other 21 patients discontinued treatment due to disease progression (n=13; 50%), adverse events (AEs; n=6; 23%), or other reasons (n=2; 8%).

After a median follow-up of 3.9 months, tumor control (defined as stable disease or better) was achieved in 73 percent of patients (n=19/26). The median time to response was 1.9 months, and the duration of response was not estimable. The median progression-free survival was 3.8 months, and the median overall survival was 20.3 months. (See the TABLE for best responses to treatment among patient subgroups.) The survival results are preliminary and could be confounded by patient selection and subsequent therapies, Dr. Ishida and co-authors wrote, and thus need to be confirmed in larger randomized trials.

Myelosuppression was the most common treatment-related grade ≥3 AE, including neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%). Serious AEs were reported in nine patients (35%) – all but two of which were resolved (one was related to thrombocytopenia and the other to acute hepatic failure). Treatment discontinuation due to AEs occurred in six patients (23%); this was most often related to neutropenia (n=2), thrombocytopenia (n=2), rash (n=1), toxic skin eruption (n=1), and acute hepatic failure (n=1). Seventeen patients (65%) underwent a dose reduction due to AEs.

No deaths were reported during the study treatment or within 28 days after the last dose of lenalidomide. Seven deaths (27%) occurred more than 28 days after the last dose of lenalidomide, six of which (23%) were related to ATLL or its complications and one (4%) was related to pneumonia unrelated to lenalidomide or ATLL. Two patients received lenalidomide for ≥52 weeks, and no secondary malignancies were reported.

“Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent ATLL, hinting at its potential to become a treatment option in this patient population,” the authors concluded.

Dr. Ishida mentioned the possibility that “this study did not include some of the patients with very aggressive and fast-growing disease. This is because, among those patients in a clinical trial setting, it is not feasible to secure four weeks of drug washout-time according to the study protocol.” Other limitations include the small study size and limited follow-up.


Reference

Ishida T, Fujiwara H, Nosaka K, et al. Multicenter phase II study of lenalidomide in relapse or recurrent adult T-cell leukemia/lymphoma: ATLL-002. J Clin Oncol. 2016;34:4086-93.

TABLE. Best Response to Lenalidomide
Population n ORR CR/CRu PR SD PD
All patients 26 11

(42%)

5

(19%)

6

(23%)

8

(31%)

7

(27%)

ATLL subtype
Acute 15 5

(33%)

3

(20%)

2

(13%)

6

(40%)

4

(27%)

Lymphoma 7 4

(57%)

2

(29%)

2

(29%)

0 3

(43%)

Unfavorable chronic 4 2

(50%)

0 2

(50%)

2

(50%)

0
Disease site
Nodal and extranodal lesions 16* 5

(31%)

5

(31%)

0 8

(50%)

2

(13%)

Skin 8 6

(75%)

4

(50%)

2
(25%)
2

(25%)

0
Peripheral blood 10 6

(60%)

4

(40%)

2

(20%)

2

(20%)

2

(20%)

At least one dose reduction
Yes 7 4

(57%)

2

(29%)

2

(29%)

3

(43%)

0
No 19 7

(37%)

3

(16%)

4

(21%)

5

(26%)

7

(37%)

Prior mogamulizumab treatment
Yes 11 2

(18%)

1

(9%)

1

(9%)

6

(55%)

3

(27%)

No 15 9

(60%)

4

(27%)

5

(33%)

2

(13%)

4

(27%)

ORR = overall response rate; CR = complete response; CRu = complete response unconfirmed;

PR = partial response; SD = stable disease; PD = progressive disease; ATLL = adult T-cell leukemia/lymphoma

*Response for one patient was not evaluable.

SHARE