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2019-07-10T08:53:32.000Z

ICML 2019: Randomized phase III study of lenalidomide/R-CHOP (R2-CHOP) vs placebo/R-CHOP in previously untreated ABC-type DLBCL

Jul 10, 2019
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On Wednesday 19 June at the International Conference on Malignant Lymphoma, Lugano, CH, Professor Umberto Vitolo, presented the first report of the global ROBUST phase III randomized trial (NCT02285062) of lenalidomide/R-CHOP (R2-CHOP) vs placebo/R-CHOP in previously untreated CD20+ activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

In the double-blind trial, investigators sought to determine whether the addition of lenalidomide to R-CHOP could improve outcomes compared with R-CHOP in 570 patients with ABC-type DLBCL. The study did not meet its primary endpoint of progression-free survival (PFS)   for R2-CHOP versus placebo/ R-CHOP as frontline therapy in patients with ABC-type DLBCL.

Patient characteristics and methods

  • N = 570 patients with ABC‐DLBCL
  • Primary endpoint: PFS by central review (per 2014 IWG)
  • Secondary endpoints included complete response (CR) rate, duration of response, time to next lymphoma treatment, objective response rate (ORR), event-free survival (EFS), overall survival (OS), and health-related quality of life
  • Histologically confirmed CD20+ DLBCL, ABC subtyping by NanoString, PS <=2
  • Baseline characteristics were generally similar between groups and the stratification factors were balanced (Table 1)
  • Median time from diagnosis to treatment: 31 days (both groups)
Table 1. Patient demographics and baseline characteristics (ITT population)

N (%)

 

R2-CHOP
(n =285)

Placebo/R2-CHOP
(n = 285)

International Prognostic Index  (IPI) score


 

2

121 (42)

120 (42)

≥3

164 (58)

165 (58)

Bulky disease

≥7 cm*

97 (34)

99 (35)

Median age, y (range)

≥ 65 y*

 

65 (21–82)

147 (52)

65 (28–83)

148 (52)

Male/female

 

164 (58)/121 (42)

143 (50)/142 (50)

ECOG performance status

0

129 (45)

111 (39)

1

104 (36)

118 (41)

2

52 (18)

56 (20)

Ann Arbor disease stage

II

37 (13)

33 (12)†

III

80 (28)

98 (34)

IV

168 (59)

154 (54)

Elevated LDH (> 234 U/L)

 

177 (62)

176 (62)

Geographic distribution

Europe

124 (44)

150 (53)

Asia-Pacific

111 (39)

92 (33)

North America

24 (8)

23 (8)

Other

26 (9)

20 (7)

Figure 1: Robust study design
Figure 1: Robust study design

Results

  • Median follow-up: 27.1 months (range 0–47)
  • PFS (primary endpoint) was not met: HR = 0.85 (89% CI, 0.63–1.14), P = 0.29 (median PFS not reached for either arm)
  • ORR was 91% for both arms: 69% vs 65% CR for R2‐CHOP vs placebo/R‐CHOP
  • In a subgroup analysis of PFS, a positive trend supporting R2‐CHOP over placebo/R‐CHOP was observed in patients with: IPI score ≥ 3 (HR = 0.74 [95% CI, 0.53‐1.05] P = 0.09)
  • 2-year OS was 79% for R2‐CHOP and 80% for placebo/R‐CHOP (median OS not reached for either arm)
  • Non-statistically significant trends favoring R2-CHOP were observed in subgroups of patients with disease stage III/IV (HR 0.81; 95% CI, 0.60–10)
  • The most common grade 3/4 AEs occurring in ≥10% of patients for R2-CHOP vs placebo/R‐CHOP were:
    • Neutropenia (60% vs 48%)]
    • Anemia (22% vs 14%)
    • Thrombocytopenia (17% vs 11%)
    • Leukopenia (14% vs 15%)
    • Febrile neutropenia (14% vs 9%), and
    • Lymphopenia (11% vs 8%)

Conclusion

The ROBUST trial was the first study to compare R2-CHOP with placebo/R‐CHOP in patients with previously untreated, prospectively selected, CD20+ ABC‐type DLBCL. Prof Vitolo concluded that overall, the ROBUST trial did not meet the PFS primary or key secondary endpoint for R2-CHOP vs placebo/R-CHOP. However, an encouraging trend for PFS supporting R2-CHOP was observed in patients with higher risk IPI ≥ 3. Prof Vitolo emphasized that analyses of ROBUST are still ongoing and future analyses will include the evaluation of pharmacokinetics/dosing, molecular classification, and mutational status.

Future clinical trials will investigate next-generation immunomodulatory agents for DLBCL.

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