|
ated in patients with a variety of lymphoma subtypes and multiple myeloma ( MM ).
In this open-label , dose-escalation , cohort-expansion study , Alexander M . Lesokhin , MD , of Memorial Sloan Kettering Cancer Center in New York , and authors evaluated the safety and efficacy of nivolumab monotherapy in 81 patients with various hematologic malignancies , including :
• 10 with follicular lymphoma ( FL )
• 11 with diffuse large B-cell lymphoma ( DLBCL )
• 10 with other B-cell lymphomas
• 13 with mycosis fungoides ( MF )
• 5 with peripheral T-cell lymphoma ( n = 5 )
• 5 with other T-cell lymphomas
• 27 with MM
Adult patients were eligible for the study if they had an Eastern Cooperative Oncology Group performance status of 0-1 with detectable or measurable disease and had received at least one prior chemotherapy regimen . Patients were excluded if they had central nervous system involvement , concomitant secondary malignancies , active autoimmune disease , prior transplantation ,
|
prior treatment with immune checkpoint antibodies , or concurrent treatment with receptor activators of nuclear factor-кB ligand inhibitors .
Patients were enrolled between August 2012 and April 2015 . The median number of prior systemic treatment regimens was three ( range = 1-12 regimens ).
During the dose-escalation phase , patients were treated with 1 mg / kg or 3 mg / kg of nivolumab as a one-hour infusion at weeks one and four , then every two weeks for up to two years until disease progression , unacceptable toxicity , or complete response . The maximum-tolerated dose was not reached , so patients in the cohort expansion were treated with 3 mg / kg of nivolumab .
The overall median follow-up was 66.6 weeks ( range = 6-81.6 weeks ), and durations of response ranged from six to 81.6 weeks . ( See TABLE 2 for response rates associated with nivolumab .)
“ With continued nivolumab therapy , the depth of objective responses may improve as demonstrated by one patient with DLBCL with an initial partial response ( at 16 weeks ) that converted to a complete response ( at 72 weeks ) with extended treatment ,” the authors wrote . “ Response durations exceeded one year for two ( one each with FL and DLBCL ) of three patients who achieved a complete response and six months for patients with FL who achieved a partial response .”
|
All patients with non-Hodgkin lymphoma ( NHL ) and MM who received at least one dose of nivolumab monotherapy were included in the safety evaluation ( primary endpoint ) and anti-tumor activity analysis ( secondary endpoint ).
Sixty-five percent of patients experienced treatment-related adverse events ( AEs ; n = 53 ), most of which were grade 1 or 2 . However , 15 of these ( 18 %) were grade 3 AEs , two had grade 4 AEs , and one had a grade 5 AE .
Immune-mediated AEs occurred in 34 percent of patients ( n = 28 ), and again , most of these were grade 1 or 2 . These AEs responded without treatment or interruption of nivolumab in 46 percent of patients ( n = 13 ); 15 patients required treatment for these AEs , five of whom had to discontinue nivolumab .
Overall , 15 percent of patients ( n = 12 ) discontinued nivolumab due to AEs . One death occurred due to fatal pneumonitis in a 51-year-old woman with small lymphocytic B-cell lymphoma .
Fluorescent in situ hybridization ( FISH ) was performed in 27 patients to evaluate the tumor cells and immune-infiltrating cells for expression of immunemodulating proteins , including PD-L1 and PD-L2 . Genetic alterations within the 9p24 locus were detected in three patients . “ Genetic alterations of PD-L1 and PD-L2 were rare among the NHLs evaluated in this study – a stark contrast to the frequent 9p24.1 alterations in HLs [ from
|
previous studies ],” the authors wrote . Analysis of immunohistochemical staining also revealed that “ PD-L1 and , to a lesser extent , PD-L2 proteins were expressed by nonmalignant cells within the tumor microenvironment in NHLs , including certain FLs .”
“ These data highlight the likely differences in the frequency of 9p24.1 alterations and associated expression of the PD-1 ligands in specific lymphoid malignancies ,” they concluded . A phase II study is ongoing to assess the role of the PD-L1 and PD-L2 biomarkers as predictors of response to nivolumab in patients with DLBCL and FL .
“ Nivolumab may have some activity in NHLs , specifically in FL , DLBCL , and some subsets of T-cell lymphoma ,” Dr . Lesokhin told ASH Clinical News . “ These early results are encouraging , but at this point it is probably too early to say how this therapy will ultimately fit in with current treatment paradigms for various subtypes of NHL .”
Dr . Lesokhin also discussed the limitations of the study , noting , “ this trial was an initial safety study in a variety of different blood cancers , [ and ] the patient populations are quite heterogeneous . Thus , definitive conclusions about single agent efficacy cannot be made .”
REFERENCE
Lesokhin AM , Ansell SM , Armand P , et al . Nivolumab in patients with relapsed or refractory hematologic malignancy : Preliminary results of a phase Ib study . J Clin Oncol . 2016 June 6 . [ Epub ahead of print ]
|