English to Russian Medical Medical: Pharmaceuticals

The principal evidence for the clinical efficacy of inotuzumab ozogamicin in patients with relapsed or refractory B-cell ALL is derived from Pfizer-sponsored studies, including a pivotal Phase 3 randomized Study B1931022 (hereafter referred to as Study B1931022, in which Salvage 1 and 2 patients were enrolled) and a supportive Phase 1/2 single-arm Study B1931010 (hereafter referred to as Study B1931010, which included more heavily treated patients).
This improvement was also consistent across all pre-specified stratification subgroups (duration of first remission, line of salvage, and age at randomization).
Overall, considering the lethal nature of relapsed and refractory B-cell precursor ALL and the limited effective treatments available with the only curative treatment option being HSCT, the clinically meaningful and statistically significant improvement in CR/CRi, the clinically meaningful improvement in OS, and greater opportunity to proceed to HSCT compared with standard of care after salvage therapy is encouraging.
The median survival time in adults with relapsed or refractory B-cell was reported to be approximately 3-6 months., Attaining a CR with first salvage therapy has been found to significantly influence patient survival, with a median survival of 1 year versus 5 months when a CR is not achieved.
Despite the associated mortality and morbidity, allogeneic HSCT after salvage therapy offers the best opportunity for long-term survival in patients with a suitable donor and a response to salvage therapy.
However, the prognosis for these patients remains poor with only approximately 30% of patients expected to have a CR after first salvage therapy with a median OS of approximately 5 months and with only a quarter of patients alive at 1 year.
Complete responses and prognosis are even poorer in the second and third salvage treatment settings.
In the LALA-94 trial, patients aged 15-55 years (Ph- and Ph+) with Bcell ALL who achieved CR followed by first relapse were treated with different salvage therapies based on Investigator’s choice; the salvage therapy options included combination chemotherapy, a first or second HSCT, or donor lymphocyte infusions.
In a study examining the outcome of 288 adult patients between 14-76 years of age with refractory or recurrent ALL who were receiving second salvage therapy, 53/288 patients (18%) achieved a CR.
Only 22 patients (8%) were able to undergo allogeneic HSCT as second salvage therapy and their 1-year survival rate was 18%.
In a review examining the prognosis in 245 adult patients between 16-81 years of age with refractory or recurrent ALL who were receiving first salvage therapy, 75/245 patients (31%) achieved a CR.
In a retrospective analysis of 224 out of 547 adult patients with ALL between 15 and 55 years of age, the CR rate was 46% after first salvage chemotherapy (chosen by the local physician) in patients who had Ph- B-cell ALL without central nervous system (CNS) involvement, no isolated extramedullary disease (EMD) and no prior HSCT.
In relapsed patients after HSCT (n=24), the CR rate after first salvage was 25% (a significantly higher proportion of patients with relapse after HSCT had high-risk features).
Although the patient population was small, the high response rate and acceptable toxicities have led to this being a commonly used salvage regimen.
Accelerated approval based on CR/CRi rate in single-arm trial of 185 adults (17.3% had received >2 prior salvage therapies)
Study B1931022 is a randomized, open-label, multicenter, global study of inotuzumab ozogamicin compared with control in adult patients with relapsed or refractory CD-positive B-cell ALL in Salvage 1 or 2 (ie, after treatment failure or relapse with 1 or 2 prior systemic therapies).
Eligible patients were male or female, 18 years or older, with relapsed or refractory CD22-positive ALL due to receive either Salvage 1 or Salvage 2 therapy and for which either arm of randomized study therapy offers a reasonable treatment option.
Patients in Salvage 1 with late relapse were to be deemed poor candidates for reinduction with initial therapy and Ph+ ALL patients were to have failed treatment with at least 1 second or third generation TKI and standard multi-agent induction chemotherapy.
Randomization was stratified by 3 factors: duration of first remission (