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 lenalidomide 25 mg / day in the multicenter , singlearm , 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 TABLE 2 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 because , among those patients in a clinical trial setting , it is not feasible to secure four weeks of drug washout-time [ per ] 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 .

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 %)