Page 71 - Haematologica Vol. 107 - September 2022

ARTICLE - Outcome of r/r B-ALL with extramedullary disease S. Kayser et al.
expression, but this remains to be elucidated in larger studies. Recent data from the INO-VATE trial suggest that patients with high (≥90%) CD22 expression levels had a higher CR rate compared to those with <90% expression (42.1% [n=45/107] vs. 20% [n=7/35]).38 According to the European Medicine Agency label, CD22 expression needs to be above 0%, thus also including patients with very dim CD22 expression levels. In the USA, the Food & Drug Ad- ministration did not specific any particular CD22 ex- pression.
Lineage switch (myeloid conversion), described mostly in patients receiving chimeric antigen receptor T-cell ther- apy, does not seem to involve CD22 expression: the antigen is maintained in intermediate phenotype relapses, suggesting that simultaneous pressure on CD19 and CD22 might avoid this mechanism of resistance.39
Increased exposure to INO has been associated with an increased risk of VOD/SOS following allogeneic HSCT, leading to the recommendation that patients being treated with INO as a bridge to allogeneic HSCT should be treated with two or fewer cycles of the drug (3 cycles if necessary to achieve a measurable residual disease- negative CR/CRi).40-42 In our cohort, VOD/SOS occurred in only three patients, including one after allogeneic HSCT, although up to four INO cycles were administered prior to transplantation. These data compare favorably to pre- viously reported data.15
Our analysis has several limitations. Since this is a retro- spective, non-randomized cohort analysis no direct com- parison to outcome of r/r ALL with EMD after standard-of-care chemotherapy treatment was feasible. However, since all patients were heavily pretreated with intensive chemotherapy including prior allogeneic HSCT in 58% of the patients, we believe that standard-of-care chemotherapy would have failed to induce a remission. The overall prognosis remains poor even if patients could be successfully bridged to allogeneic HSCT, strongly ar- guing for alternative consolidation approaches, such as chimeric antigen receptor T cells or advanced bi-specific
References
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antibodies.43 Nevertheless, the ability of INO to be given in an outpatient setting with few toxicities may continue to make it a valuable possibility in the treatment of B-ALL. In conclusion, this outcome analysis demonstrates that treatment with INO is an effective and promising ap- proach in r/r ALL patients with EMD. The CD22 status should be routinely assessed at diagnosis and r/r B-ALL patients, in order to evaluate the indication for INO treat- ment better. However, allogenic HSCT alone seems not to be effective in maintaining disease control. Thus, chimeric antigen receptor T cells or advanced bi-specific anti- bodies as consolidation therapy should be evaluated in the future.
Disclosures
No conflicts of interest to disclose.
Contributions
SK and RFS were responsible for the concept of this study, contributed to the literature search, collection, analysis and interpretation of the data, and wrote the manuscript. CP was responsible for the concept of the study, con- tributed to the literature search and data collection, con- tributed patients, analyzed and interpreted data, and critically revised the manuscript. NP analyzed and inter- preted data. CS, MRL JW, FG, AMB, MF, CL, DW, ADH and MJL contributed patients and critically revised the manu- script. All authors reviewed and approved the final version of the manuscript.
Funding
SK was supported by the Olympia-Morata fellowship pro- gram from the Medical Faculty of Heidelberg University. We acknowledge publication support from Leipzig University.
Data-sharing statement
Questions regarding data sharing should be addressed to the corresponding author.
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