ASH 2019: Blinatumomab instead of chemotherapy as post-reinduction therapy in HR/IR first relapse B-ALL in children and young adults: report from the GOG AALL1331 study (LBA-1)
ALL Patients between the age of 1-30 and at HR/IR first relapse were enrolled and after the first month of chemotherapy were randomised to either receive more chemotherapy or blinatumomab, before going onto bone marrow transplant.
Prof. Brown reports that the experimental arm of blinatumomab showed approximately a 20% improvement in "Disease Free Survival and in Overall Survival, establishing a new standard of care for patients who have generally a poor outcome".
The ability of blinatumomab to successfully bridge to HSCT might be a relevant contributor to the improved survival for Arm B (blinatumomab) vs. Arm A (chemotherapy) in HR/IR relapses.
An interview from Prof. Patrick Brown at ASH 2019 to these study results can be viewed here
ASH 2019: Real-World data of Blinatumomab in adult and pediatric B-ALL patients
In this large real-world cohort, encouraging efficacy of Blinatumomab was seen in patients with R/R B-ALL and MRD positive B-ALL patients (adults as well as in children). (NEUF-study, Boissel et al., abstr. 2627 and 2624; Locatelli F, et al., abstr. 1294)
The corresponding posters are available here
ASH 2019: Blinatumomab + Dasatinib in adult patients with Ph+ B-ALL: updates of the D-ALBA trial. (abstr. 740)
Blinatumomab plus Dasatinib as chemotherapy-free induction-consolidation protocol in adult patients with Ph+ B-ALL showed promising results with high molecular response rates and survival rates.
presentation by S. Chiaretti is available for download here
EHA 2019: Blinatumomab in MDR+ BCP-ALL: mOS not reached at 5 years in complete responders
EHA 2019: results of the GIMENA LAL2116 D-ALBA trial: Blinatumumab-Dasatinib as FL in Ph+ ALL.
ASH 2018: Long-term benefit of Blinatumomab in MDR+ BCP-ALL: update of BLAST
Long-term benefit of Blinatumomab in MDR+ ALL: BLAST study update
(N. Goekbuget et al. ASH 2018)
During the Oral presentation, N. Goekbuget showed that the median Overall survival is not reached in patients who achieved a complete MRD response with a median follow-up of about 4.5 years.
These results further support the long-term benefits associated with Blinatumomab and MRD response.
ASH 2018: Hyper-CVAD + Blinatumomab as frontline therapy in B-ALL: a phase 2 study
hyper-CVAD +Blinatumomab consolidation in B-ALL
(Richard-Carpentier et al. ASH 2018)
An MRD-negativity rate of 93%, 1-yr OS rate of 90%, and 1-yr RFS rate of 77% were observed.
ASH 2018: SWOG 1318 - Blinatumomab mono-induction plus POMP maintenance in newly diagnosed B-ALL.
Blinatumomab monotherapy induction in B-ALL: SWOG 1318
(Advani et al. ASH 2018)
A. Advani showed in the oral presentation that in a population of elderly patients with a median age of 75 years and a baseline bone marrow blast rate of 86.5%, single-agent induction with blinatumomab resulted in a 71% rate of MRD negativity with a 1-year OS of 65% & DFS 55%.
ASH 2018: Effect of Blinatumomab on Health-related Quality of Life in ALL
Blinatumomab and HRQoL: two posters
(Zugmaier et al. Abstract #1377; Stein et al. Abstract #3967; ASH 2018)
In the BLAST Study, Patients with MRD positive B-cell ALL had a trend toward better HRQoL at baseline compared with R/R ALL. In patients with B-cell precursor ALL and MRD treated with blinatumomab, HRQoL was maintained during and after treatment – This is a noteworthy observation considering the potential HRQoL impact of standard chemotherapy.
In the HRQoL subgroup analysis of the TOWER study, HRQoL was maintained or improved for patients treated with blinatumomab versus chemotherapy, even more so for patients with high disease burden. Blinatumomab delayed time to HRQoL deterioration compared with chemotherapy, and the treatment effects were particularly larger among patients with high disease burden.
ASH 2018: Blinatumomab in pediatric ALL: update of the RIALTO Expanded Access study
Blinatumomab induced MRD response in almost half of the patients, including patients with t(17;19) or prior blinatumomab treatment. The data support Blinatumomab as a treatment option for pediatric patients with r/r ALL. Poster was presented by F. Locatelli (Abstract # 1375).
ASH 2018: Blinatumomab in Diffuse Large B-Cell Lymphoma: a phase 2 study
Study of Blinatumomab in DLBCL
(Coyle et al. ASH 2018)
At baseline about 68% of patients were double refractory; 66% had progressive disease after salvage therapy 1. Blinatumomab monotherapy as 2nd salvage resulted in an ORR of 37%; complete molecular remission in 22% of patients; 20% of patients proceeded to HSCT.
According to the authors, the study demonstrated a clinically meaningful efficacy of Blinatumomab in patients with highly aggressive r/r B-NHL.
ASCO and EHA 2018
Three analyses of Blinatumomab in relapsed/refractory ALL were presented:
Long term survival after Blinatumomab and subsequent alloHSCT
(Topp et al. Abstract 7044, ASCO 2018)
Topp et al. analysed two Blinatumomab studies in adult Ph neg r/r ALL (TOWER) and MRD+ ALL (BLAST) on long term survival after Blinatumomab and subsequent alloHSCT. The survival rate of ≤35 yrs transplanted patients in the MRD study was 62% after an observation period of minimum 3 years vs 22% in non-transplant patients. In transplant patients >35 yrs the OS rate was 40%, vs 48% in non -transplant patients.
Authors discussed that Blinatumomab represents for this patient population a possible treatment option.
Indirect comparison between TOWER and INO-VATE
(Song et al. Abstract PF187, EHA 2018)
Patients with 2+ salvage therapies in TOWER were excluded, as not represented in INO-VATE. To ensure a balance between the remaining population, the population of TOWER was weighted, to adapt to the baseline characteristics of INO-VATE. Endpoints were OS and CR. The relative Restricted Mean Survival Time (RMST) has been determined after 12 months.
The median OS was 9.3 months for Blinatumomab and 7.7 months for Inotuzumab (weighted log-rank test p = 0.4). RMST after 12 months was 1.6 months longer for Blinatumomab than for Ino (95% CI = [0.1, 3.2], p < 0.05). CR rates were identical (anchor-based difference = -2.8%, 95% CI = [-17.5%, 11.9%], p = 0.7). The authors concluded a potential OS benefit for Blinatumomab vs Inotuzumab in adults with r/r ALL with or without prior salvage therapy.
Benefit of early treatment with Blinatumomab
(Severin et al. Abstract PS1427, EHA 2018)
Severin et al. simulated long-term survival outcomes in adults with Ph- R/R B-precursor ALL receiving blinatumomab vs salvage SOC chemotherapy, and quantified the value of Blinatumomab treatment as a first salvage therapy (early treatment) versus as a subsequent salvage therapy (late treatment), using QoL data for modeling. Calculated 5-yrs-probability of survival was 22.4% vs 10.3% for Blinatumomab vs SOC as early treatment, and 13.2% vs 7.5% as late treatment. Authors concluded that an early treatment doubled the life expectancy and the QALY.
Three analyses from TOWER study were presented:
Blinatumomab maintenance therapy after haematologic remission (Rambaldi et al. ASH 2017)
Quality of Life with Blinatumomab treatment (Topp et al. ASH 2017)
Baselines biomarkers on outcomes with Blinatumomab treatment (Wei et al. ASH 2017)
TOWER Analysis by first salvage – H. Dombret et al.
In the TOWER study improved OS and CR rates were achieved following treatment with Blinatumomab compared with SOC among patients. Improvements in OS and CR rates occurred regardless of prior salvage therapy status.
Patients with a prior salvage therapy received more frequently an alloHSCT after Blinatumomab treatment compared to the SOC.
TOWER by 1st salvage
(Dombret et al. EHA 2018)