MEETING NEWS LYMPHOMA
Brentuximab Vedotin Plus R-CHP a Frontline Treatment Option for Patients with NHL Subtypes
The CD30-directed immunoconjugate brentuximab vedotin has demonstrated efficacy in Hodgkin lymphoma ( HL ) and other T-cell lymphomas . According to research presented at the 2017 ASH Annual Meeting , brentuximab vedotin could represent a frontline option for this patient population .
In an open-label , multicenter , phase I / II study , all patients with CD30-positive B-cell non-Hodgkin lymphoma ( NHL ) responded to frontline treatment with brentuximab vedotin plus R-CHP ( rituximab , cyclophosphamide , doxorubicin , prednisone ). This included 25 patients ( 86 %) who had a complete response ( CR ; 95 % CI 72-98 ; overall response rate [ ORR ] and CR were primary endpoints of phase II ), reported lead author Jakub Svoboda , MD , of the Lymphoma Program at Penn Medicine ’ s Abramson Cancer Center in Philadelphia , and colleagues .
The trial enrolled 33 treatment-naïve patients from three centers between January 2014 and June 2017 . Patients had any Ann Arbor stage disease and at least equivocal CD30 expression on immunohistochemistry .
Phase I of the study used a 3 + 3 dose de-escalation design , with a starting dose of brentuximab vedotin 1.8 mg / kg , which was administered concurrently with R-CHP once every three weeks for a total of six cycles :
• brentuximab vedotin 1.2 mg / kg or 1.8 mg / kg on day 2 of cycle 1 , and day 1 of cycles 2-6
• rituximab 375 mg / m 2
• cyclophosphamide 750 mg / m 2
• doxorubicin 50 mg / m 2
• prednisone 100 mg
Use of granulocyte-stimulating factor was permitted per institutional practice , and consolidative radiation after post-treatment imaging was administered at physician ’ s discretion .
One patient was re-classified from grey zone lymphoma ( GZL ) to HL prior to starting therapy and another patient withdrew consent . Of the remaining 31 patients , 23 ( 74 %) had primary mediastinal large B-cell lymphoma ( PMBCL ), six ( 19 %) had diffuse large B-cell lymphoma , and two ( 7 %) had GZL . The median patient age was 37 years ( range = 18-76 years ), 74 percent ( n = 23 ) had bulky disease ( ≥7.5 cm in diameter ), and 35 percent ( n = 11 ) had stage III / IV disease .
No treatment-related deaths occurred . One patient discontinued treatment after concurrent grade 3 sepsis and left ventricular ( LV ) systolic dysfunction after cycle four . Another patient discontinued treatment because of grade 2 pneumonitis during cycle five that was deemed “ possibly related to brentuximab vedotin .”
Two patients receiving brentuximab vedotin 1.2 mg / kg required dose reductions because of sensory neuropathy . The most common grade 3 / 4 adverse events ( AEs ) included febrile neutropenia ( n = 4 ) and afebrile neutropenia ( n = 8 ). Grade 3 non-hematologic AEs that were “ possibly related ” to treatment included nausea / vomiting ( n = 1 ; 3 %) and sepsis with LV systolic dysfunction ( n = 1 ; 3 %). The most common grade 2 nonhematologic AEs were nausea ( 16 %), sensory neuropathy ( 13 %), diarrhea ( 10 %), motor neuropathy ( 6 %), and anorexia ( 6 %). One patient who had a family history of acute myeloid leukemia ( AML ) developed AML two years after completion of chemotherapy and is in remission following allogeneic hematopoietic cell transplantation .
No dose-limiting toxicities ( primary endpoint of phase I ; defined as any grade 3 / 4 non-hematologic toxicity observed in cycle 1 requiring a dose delay > 14 days from the planned day 1 of cycle 2 ) occurred . Given these results , the researchers selected the 1.8 mg / kg dose for phase II .
After a median follow-up of 15 months ( range = 5-36 months ), the ORR for 29 evaluable patients was 100 percent . Response rates by disease subtype are presented in TABLE 2 .
The median progression-free survival ( PFS ) and overall survival ( OS ; both secondary endpoints of phase II ) were not reached for those still alive at assessment . Among the full patient cohort , one-year PFS was 86 percent ( 95 % CI 63-95 ) and oneyear OS was 100 percent .
The clinical benefit appeared to be highest in the PMBCL cohort : Median PFS was not reached , and one-year PFS was 87 percent ( 95 % CI 57-97 ). Patients with stage I / II PMBCL ( n = 13 ) had a one-year PFS rate of 100 percent , while those with stage III / IV disease had a one-year PFS rate of 73 percent ( 95 % CI 23- 93 ). The authors also noted that PFS rates did not differ between
TABLE 2 . Response Rates Among Patients Treated With Brentuximab Vedotin Plus R-CHP
Total ( n = 29 ) PMBCL ( n = 22 ) DLBCL ( n = 5 ) GZL ( n = 2 ) Overall response rate 100 % 100 % 100 % 100 % Complete response rate 86 % 82 % 100 % 100 % Partial response rate 14 % 18 % - -
R-CHP = rituximab , cyclophosphamide , doxorubicin , prednisone ; PMBCL = primary mediastinal large B-cell ; DLBCL = diffuse large B-cell lymphoma ; GZL = grey zone lymphoma
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