Page 11 - Haematologica May 2022

Landmark Paper in Hematology
patients treated with VD versus D alone, despite this crossover. The combined complete and partial response rates were 38% versus 18% (P<0.001), median progres- sion-free survival was 6.22 months versus 3.49 months (hazard ratio [HR] 0.55; P<0.0001), the 1-year overall sur- vival was 80% versus 66% (HR 0.57; P=0.001) and grade 3/4 adverse events occurred in 75% versus 60%, respec- tively.2 This study led to swift approval of VD in RRMM and established that novel agents (NA), far more active than dexamethasone, should be developed. In fact, with myriads of papers in MM, numerous publications exist for RRMM, illustrating the widespread use of PI and the important follow-up studies evolving after the New England Journal of Medicine publication.2 The enormous success of APEX and its worldwide implication are exem- plified in Figure 1B and C, namely that PI were defined as key NA and induced impressive responses not only in RRMM, but also in induction, consolidation and mainte- nance, and stood at the beginning of the rapid develop- ment of several NA which have revolutionized MM treat- ment. APEX has stimulated multiple follow-up research, including papers on lines of therapy and response, earlier versus later relapse treatment, side effect management, cytogenetics/high-risk patients, PI retreatment, and avoidance and recovery of peripheral neuropathy. It allowed the exploration of multiple highly potent Bz combinations beyond D, namely employing IMiD, CTx,
References
mAb and others. It encouraged the development of sec- ond generation PI and novel PI schedules, i.e., with sub- cutaneous and weekly applications, rather than intra- venous and twice a week applications. It has demonstrat- ed that NA are a vital treatment armamentarium that has even challenged the replacement of standard autologous stem cell transplantation with NA treatment alone.
Disclosures
The authors participated in the APEX study at the University of Freiburg (UKF) / Comprehensive Cancer Center Freiburg (CCCF), but other than receiving study support (UKF/CCCF) for the patients being included and meticulously documented in APEX, declare no competing financial interest related to this his- toric report.
Contributions
ME wrote this report, JMW and RW provided comments and approved the paper.
Acknowledgements
The authors thank distinguished IMWG, EMN, DSMM and GMMG experts for their advice and recommendations. We apologize that only a fraction of important papers, related to the APEX study can be cited. The paper is dedicated to all MM experts worldwide, our MM patients and all colleagues involved in clinical studies and industry.
1. Lohr JG, Stojanov P, Carter SL, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25(1):91-101.
2.Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487-2498.
3. Orlowski RZ. The ubiquitin proteasome pathway from bench to bedside. Hematology Am Soc Hematol Educ Program. 2005;220-225.
haematologica | 2022; 107(5)
1019