Combination of Lemzoparlimab Plus Azacitidine Shows Promise in Newly Diagnosed Higher-Risk MDS

The combination of lemzoparlimab and azacitidine continues to show promise in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS), according to an ongoing phase II trial.

The results of the trial were presented during the 2022 European Society for Medical Oncology (ESMO) Congress by Chunkang Chang, MD, PhD, of the Department of Hematology at Shanghai Sixth People’s Hospital, and leading principal investigator of the study.

The treatment demonstrated “clinically meaningful efficacy results,” and the effect was prominent without a priming dose of lemzoparlimab, according to Dr. Chang and colleagues.

The study enrolled 53 patients with untreated intermediate or high-risk MDS according to the International Prognostic Scoring System (IPSS-R). The median patient age was 65 years (range, 40-80 years). At baseline, 79.2% of patients had a high/very high IPSS-R score, 87% had excess blasts, and 13.2% had a TP53 mutation.

Patients received lemzoparlimab 30 mg/kg weekly intravenously and azacitidine 75 mg/m² subcutaneously on days one to seven in a 28-day cycle. Efficacy was assessed by the International Working Group 2006 criteria.

The trial measured the overall response rates (ORRs), including the rates of complete remission (CR), marrow complete remission (mCR) with hematologic improvement (HI), as well as the rates of stable disease (SD) and progressive disease (PD) at three different evaluation times (see TABLE 1 for responses).

TABLE 1. Responses at Three Different Evaluation Times
Best response	Time since first dose (evaluable patients, N=47)
	≥3 months (N=36)	≥4 months (N=29)	≥6 months (N=15)
ORR	80.6%	86.2%	86.7%
CR	27.8%	31%	40%
mCR with HI	13.9%	17.2%	13.3%
mCR	30.6%	27.6%	20%
HI	8.3%	10.3%	13.3%
SD	16.7%	10.3%	13.3%
PD	2.8%	3.4%	0%

 

“For patients enrolled three months or longer before analysis, the ORR response is 81%,” Dr. Chang said. “For patients enrolled six months or earlier, the overall response is 87%. [The] CR rate is 40%, and follow-up for all patients remain ongoing.”

For the patients achieving CR after treatment, the frequency of MDS-related gene mutations such as TP53, TET2, and RUNX1 “significantly decreased,” Dr. Chang noted, with 56% of patients achieving minimal residual disease negativity (<10^-4) by flow cytometry.

“The clinical activity seen with lemzoparlimab in combination with [azacitidine] thus far, in addition to the favorable safety profile, continues to show promise in this difficult-to-treat patient population,” said Dr. Chang. “Lemzoparlimab represents a potentially important novel treatment option for patients with [high-risk] MDS as well as many other hematological malignancies.”

This study was funded by I-Mab biopharma.