en-label,multicenter clinical trial that included a cohort of 80 patients with relapsed or refractory DLBCLafter least one prior regimen. Patients were randomized 1:1 to receive either POLIVY incombination with bendamustine and a rituximab product (BR) or BR alone for six 21-day cycles.
Randomization was stratified by duration of response (DOR) to last therapy. Eligible patientswere not candidates for autologous HSCT at study entry. The study excluded patients withGrade 2 or higher peripheral neuropathy, prior allogeneic HSCT, active central nervous systemlymphoma, or transformed lymphoma.
Following premedication with an antihistamine and antipyretic, POLIVY was given byintravenous infusion at 1.8 mg/kg on Day 2 of Cycle 1 and on Day 1 of Cycles 2–6.
Bendamustine was administered at 90 mg/m2intravenously daily on Days 2 and 3 of Cycle 1 andon Days 1 and 2 of Cycles 2–6. A rituximab product was administered at a dose of 375 mg/m2intravenously on Day 1 of Cycles 1–6. The cycle length was 21 days.
Of the 80 patients randomized to receive POLIVY plus BR (n = 40) or BR alone (n = 40), themedian age was 69 years (range: 30–86 years), 66% were male, and 71% were white. Most
patients (98%) had DLBCL not otherwise specified. The primary reasons patients were notcandidates for HSCT included age (40%), insufficient response to salvage therapy (26%), andprior transplant failure (20%). The median number of prior therapies was 2 (range: 1–7), with29% receiving one prior therapy, 25% receiving 2 prior therapies, and 46% receiving 3 or moreprior therapies. Eighty percent of patients had refractory disease to last therapy.
In the POLIVY plus BR arm, patients received a median of 5 cycles, with 49% receiving6 cycles. In the BR arm, patients received a median of 3 cycles, with 23% receiving 6 cycles.
Efficacy was based on complete response (CR) rate at the end of treatment and DOR, asdetermined by an independent review committee (IRC). Other efficacy measures included IRCassessedbest overall response.
Response rates are summarized in Table 7.
Table 7 Response Rates in Patients with Relapsed or Refractory DLBCL
Response per IRC, n (%)a
POLIVY + BR BR
n = 40 n = 40
Objective Response at End of Treatmentb
(95% CI)
18 (45)
(29, 62)
7 (18)
(7, 33)
CR
(95% CI)
16 (40)
(25, 57)
7 (18)
(7, 33)
Difference in CR rates, % (95% CI)c 22 (3, 41)
Best Overall Response of CR or PRd
(95% CI)
25 (63)
(46, 77)
10 (25)
(13, 41)
Best Response of CR
(95% CI)
20 (50)
(34, 66)
9 (23)
(11, 38)
PR = partial remission.
a PET-CT based response per modified Lugano 2014 criteria. Bone marrow confirmation of PET-CT CRwas required. PET-CT PR required meeting both PET criteria and CT criteria for PR.
b End of treatment was defined as 6–8 weeks after Day 1 of Cycle 6 or last study treatment.
c Miettinen-Nurminen method
d PET-CT results were prioritized over CT results.
In the POLIVY plus BR arm, of the 25 patients who achieved a partial or complete response,16 (64%) had a DOR of at least 6 months, and 12 (48%) had a DOR of at least 12 months. In the BR arm, of the 10 patients who achieved a partial or complete response, 3 (30%) had a DORlasting at least 6 months, and 2 (20%) had a DOR lasting at least 12 months.
15 REFERENCES
1. “OSHA Hazardous
Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html]
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
PO |
