Long-term outcomes of inotuzumab ozogamicin plus allo-HSCT conditioning regimen in CD22+ lymphoid malignancies

Inotuzumab ozogamicin (InO) is an anti-CD22 monoclonal antibody that has demonstrated anti-tumor activity and manageable safety in patients with B-cell acute lymphoblastic leukemia (ALL) and lymphoma; however, it is associated with veno-occlusive disease, particularly in patients undergoing allogeneic stem cell transplantation (allo-SCT) receiving two-alkylating agent conditioning regimen or those with an elevated bilirubin level at or above the upper limit of normal pre-SCT.¹

Here, we summarize a presentation by Khouri from the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, on the long-term survival results of InO plus an allo-HSCT conditioning regimen in patients with relapsed/refractory CD22⁺ lymphoid malignancies.

Study methods

This study included patients aged 18–70 years with relapsed/refractory chronic lymphocytic leukemia or non-Hodgkin lymphoma (NHL) who had an Eastern Cooperative Oncology Group Performance Status of ≤2, serum bilirubin <2 mg/dL, and alanine transaminase (AST) <2 times the upper limit of normal.

InO was given on Day 13 prior to the one-alkylator containing conditioning regimen of bendamustine/fludarabine/rituximab (BFR). Patients received tacrolimus and methotrexate for graft-versus-host disease (GvHD) prophylaxis.

Results

In total, 26 patients were included in the study; baseline characteristics are summarized in Table 1.

Table 1. Baseline characteristics*

Characteristic, % (unless otherwise stated)	InO + BFR (N = 26)
Median age (range), years	59 (26–70)
≥60 years	46
HCT-CI ≥3	42
Histology
CLL	42
MCL	31
FL	19
DLBCL	8
Median prior lines of therapies (range), n	2.5 (1−6)
Prior autologous transplant	4
Prior therapies
Ibrutinib	38
Venetoclax	19
Idelalisib	8
Nivolumab	4
CAR T cell	4
Disease status at transplant
CR	69
PR	27
SD	4
InO dose level
0.6 mg/m2	15
1.2 mg/m2	8
1.86 mg/m2	77
Donor type
MUD	58
MSD	42
BFR, bendamustine, fludarabine, rituximab; CAR, chimeric antigen receptor; CLL, chronic lymphocytic leukemia; CR, complete remission; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HCT-CI, hematopoietic cell transplantation – comorbidity index; InO, inotuzumab ozogamicin; MCL, mantle cell lymphoma; MUD, matched unrelated donor; MSD, matched sibling donor; PR, partial response; SD, stable disease. *Data from Khouri.1

Graft-versus-host disease, treatment-related mortality, and response rates

Overall, 42% of patients did not have an absolute neutrophil count of <0.5 × 10⁹/L, and 77% did not have a platelet count of <20 × 10⁹/L. All patients had donor cell engraftment, with a median absolute neutrophil count recovery of 6.5 days and a median platelet recovery of 0 days.

Grade 2–4 acute GvHD occurred in 27% of patients, with Grade 3–4 in only 4%. The incidence of chronic GvHD was 50%. The 1- and 5-year treatment-related mortality was 12%.

Of the seven patients with chronic lymphocytic leukemia who had a partial response and stable disease at study entry, six achieved a CR post-allo-HSCT, with four patients achieving MRD-negativity. Among the four patients with CR at the time of transplant, three attained MRD negativity.

Survival and toxicities

At the median follow-up of 48.7 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 84% and 80%, respectively. For patients receiving matched sibling donors (MSD) vs those with matched unrelated donors, the OS was 100% vs 72%, respectively; and the PFS was 100% vs 64%, respectively. There was a total of four deaths in study, due to acute GvHD (n = 2), cGvHD (n = 1), and progressive disease (n = 1).

Comparison analysis

For the comparison analysis between the BFR + InO study group and the historical control group (N = 56), there were no differences in the patient characteristics. Overall, there was a trend towards a better OS and PFS for patients with CD22⁺ NHL in the study vs the control group (Figure 1).

There was one case of veno-occlusive disease reported in the study group. Grade 1 AST increase was seen in nine patients within the control group and one patient in the study group; and Grade 2 AST increase was seen in one patient in each of the control and study group. Grade 1 and 2 bilirubin increase occurred in five and two patients, respectively, within the control group; and one patient each experienced Grade 1, 2, and 3 bilirubin increase in the study group.

OS, overall survival; PFS, progression-free survival.
*Adapted from Khouri.¹

Presenter’s conclusion

This study showed that InO combined with BFR is a safe regimen that may improve survival outcomes for patients with CD22⁺ NHL; however, these data need to be validated in a larger cohort. Additional studies are ongoing investigating the efficacy and safety of InO with posttransplant cyclophosphamide to reduce the risk of GvHD in patients with CD22⁺ diseases, such as those with ALL undergoing HSCT.