Blinatumomab continues to prevail over CT for ALL

Two trials presented at ASH 2020 reflect the immuno-oncotherapeutic benefit of the BiTE^®* molecule blinatumomab in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL).

High-risk first relapse BCP-ALL

In one study, following induction therapy and two cycles of high-risk consolidation chemotherapy (CT), 108 children were randomized 1:1 to receive a third consolidation course with either blinatumomab 15 µg/m²/day for 4 weeks or CT**. A majority of participants completed treatment (91 percent [blinatumomab] and 89 percent [CT]). [ASH 2020, abstract 268]

There were fewer blinatumomab vs CT recipients who reported events (33 percent vs 57 percent; median event free survival [EFS], not reached vs 7.4 months). The risk of relapse was also reduced by 64 percent with blinatumomab vs CT (hazard ratio [HR], 0.36; p<0.001).

Moreover, overall survival (OS) favoured blinatumomab over CT (HR, 0.43). The fraction of participants achieving MRD*** remission (MRD <10^-4) was greater with blinatumomab vs CT (94 percent vs 54 percent).

The incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was higher with CT vs blinatumomab (80 percent vs 57 percent). “[However,] as expected, grade ≥3 neurologic events occurred more frequently with blinatumomab than with CT,” noted presenting author Dr Franco Locatelli from the IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. “[Nonetheless,] no grade ≥3 cytokine release syndrome events were reported.”

Taken together, these findings show that pre-alloHSCT^# consolidation therapy with blinatumomab led to a markedly better EFS, lower recurrence risk, and fewer grade ≥3 TEAEs than CT in children with high-risk first-relapse BCP-ALL, said Locatelli.

RIALTO: Relapsed/refractory BCP-ALL

The open-label expanded access RIALTO trial saw 110 children (median age 8.5 years, 11 percent with <5 percent blasts but with MRD ≥10⁻³, 61 percent with <50 percent blasts) with relapsed/refractory (R/R)^## CD19+ BCP-ALL. Blinatumomab was given as a continuous, 6-week (4 weeks on, 2 weeks off) infusion for up to 5 cycles. Children with <25 percent blasts were given a dose of 15 µg/m²/day, while those with ≥25 percent blasts received a dose of 5 µg/m²/day (days 1–7 of cycle 1) followed by 15 µg/m²/day. [ASH 2020, abstract 977]

During the first two cycles, complete response (CR) with an MRD response was achieved by 11 of 12 patients with <5 percent blasts, and 46 of 98 patients with ≥5 percent blasts at baseline.

Among those who were able to proceed with HSCT after achieving CR, nine were from the group with <5 percent blasts, while 36 came from those who had ≥5 percent blasts at baseline.

Overall CR rate was 62.7 percent.

Of those who achieved CR, median relapse-free survival (RFS) remained unchanged at 8.5 months. More than a third (38 percent) relapsed, while 9 percent died. At 12 months, RFS was more favourable for children who received HSCT after blinatumomab (70 percent) compared with those who did not (30 percent) which, according to Locatelli, correlates with data from the primary analysis.

Median OS were 16.6 and 14.6 months in the respective groups who did and did not have HSCT prior to blinatumomab. Nearly a third (29.9 percent) were still alive at 24 months.

Almost all participants (99 percent) reported TEAEs (65 percent grade ≥3, 46 percent serious), while about three-quarters (74 percent) reported treatment-related AEs (36 percent grade ≥3, 26 percent serious).

Taken together, the safety and efficacy findings in the final analysis of RIALTO correlate with those reported in the primary analysis. [Blood Cancer J 2020;doi:10.1038/s41408-020-00342-x] “RIALTO [has initially] demonstrated that blinatumomab is effective with a manageable safety profile in children with R/R BCP-ALL … [The current findings] strengthen the observation that blinatumomab demonstrates durable efficacy and is a suitable treatment option in [this setting],” said Locatelli.

Collectively, the findings underscore the potential of blinatumomab as a new standard of care for BCP-ALL, he added.