Introduction Introduction of inotuzumab ozogamicin (InO), has changed the landscape of salvage treatment in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). A previous study has shown the feasibility and safety of InO in combination with low dose chemotherapy in patients with R/R ALL Here we present our experience in using this salvage chemotherapy regimen in our patients with R/R ALL.

Methods A single-arm, phase 2 study of adults with R/R B-cell ALL or high-risk measurable residual disease (MRD) positive prior to hematopoietic stem cell transplantation (HSCT) conducted at Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. The chemotherapy protocol consisted of mini-CVD part A (cyclophosphamide at 150mg/m2 x 4 doses, dexamethasone 20mg x 4 days, vincristine 1.5mg on day 1 and 8, but no anthracycline) or part B (methotrexate 250mg/m2 and cytarabine 0.5gm/m2 x 4 doses). InO was given at a flat dose of 1mg on day 3 of chemotherapy and additional dose was given if there were circulating blasts on day 8 peripheral smear or if there was infection prohibiting additional chemotherapy. Rituximab 375mg/m2 was added weekly to cases that had CD20>20% expression. Central nervous system (CNS) prophylaxis included methotrexate and cytarabine alternately on day 2 and day8 of each cycle. Bone marrow evaluation with (MRD) was done on day 28 of each cycle. MRD negative patients were taken up for transplant by 6 weeks if they had a donor.

Outcomes The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate.

Results A total of 24 patients were included in the study. Of these, 21 patients (87.5%) underwent HSCT. The median age was 37years (range 11-57), median WBC count was 2675/µL (range 670–168020), median bone marrow blast percentage was 35% (range 1–90%) and median LDH level was 347.5 U/L (range: 136–7580). InO-mini CVD was used in salvage 1 in 7 (29%), in salvage 2 in 10 (41%) and in 7 (29%) to achieve MRD negative status. The median number of cycles administered was 2 (Range 1-4). There were 15 males (62.5%). Central nervous system involvement was absent in 87.5% of patients.

Cytogenetic analysis showed a diploid karyotype in 7 patients (29%), normal karyotype in 8 (33%), t (9;22) is 3 and other abnormalities in 6. Three patients were TP53 positive. CD22 expression was positive in 22 patients (91.4%), Other therapies added to this regimen included tyrosine kinase inhibitors in 3 patients (12.5%), venetoclax in 13 patients (54%), and rituximab in 11 patients (45.3%).

The overall response rate (ORR) was 95.8% (n = 23). Seventeen patients (70.8%) achieved complete remission (CR), three (12.5%) had CR without platelet recovery (CRp), two (8.3%) had CR with incomplete hematologic recovery (CRi), and one (4.1%) experienced progressive disease.

Grade 3/4 toxicities included bleeding in 1, neutropenia in 2, anemia in 1, infection in 5 and hyperbilirubinemia in 2 patients.

Haploidentical transplant was performed in 15 patients, matched sibling donor (MSD) in 5, and matched unrelated donor (MUD) in 1. Conditioning regimens included Flu/TBI in 12 patients, Fludarabine (Flu)/Melphalan (Mel) in 2 patients, Flu/Mel/Total Body Irradiation (TBI) in 4 patients, Flu/Cyclophosphamide/TBI in 2 and Flu/Thiotepa/TBI in 1. Graft versus host disease prophylaxis varied, with post-transplant cyclophosphamide (PTCy) /Cyclosporine (CsA)/mycophenolate mofetil (MMF) used in 15 patients, PTCy/CSA in 5, and CSA/methotrexate in 1.

The median CD34+ stem cell dose was 6.4 ×10⁶/kg (range: 4.1–8.7). Post-transplant complications included bacteremia in 6 patients and veno-occlusive disease (VOD) in 5 patients. Cytomegalovirus reactivation occurred in 8 patients. Both acute and chronic GVHD were observed in 3 patients each and graft failure observed in 1 and 2 relapsed.

Median Over survival (OS)was 23 months (95% CI:5.09-40.91) with 1 and 2-year OS rates of 72.8% and 43.7% respectively, median follow up was-24 months and disease free survival (12) Ten patients died causes being VOD sepsis progressive disease

Conclusion: InO mini CVD is a feasible and effective salvage regimen in R/R B-ALL, offering high response rates and enabling successful bridging to transplant with manageable toxicity.

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2025
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