Startseite Kongressberichte 2020 Virtual Edition of the 25th Annual Congress of the European Hematology Association Oral Sessions Chronic Lymphoid Neoplasms CLL: CLL:

CLL - Targeted therapy II

 
Anne-Sophie Michallet, Marie Sarah DILHUYDY, Luc Matthier FORNECKER, et al.
 
The authors of the abstract conclude: 
These findings demonstrated that treatment induction with obinutuzumab and ibrutinib followed by an MRD‑driven strategy yielded a high rate of CR with BM and PB MRD <0.01%, together with prolonged PFS and OS. With longer follow-up, including assessing the evolution of PB MRD, the response is maintained. This strategy could be an option in the first‑line setting, although randomised trial evidence is needed.
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Lydia Scarfò, Silvia Bonfiglio, Lesley-Ann Sutton, et al.
 
The authors of the abstract conclude: 
This study reveals that ~50% of pts relapsing on ibrutinib had a BTK p.C481 mutation by NGS. ddPCR validated NGS analysis with 100% concordance above the pre-set threshold of 1%. Additional low-frequency BTK-mutated clones in 5 R/R cases by ddPCR were indeed present also in the NGS reads though initially disregarded  (<1% VAF in 3/5 cases). PLCG2 mutations were rare (9/59 R/R pts) and rarely isolated (2 R/R pts). There remains to dissect additional mechanisms underlying resistance to BTKi in the ~40% of pts without BTK /PLCG2 mutations. Analysis of additional genes (e.g. TP53, NOTCH1, SF3B1) is currently ongoing and will be presented at the meeting.
 
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Jacob Soumerai, Anthony Mato, Jason Carter, et al.
 
The authors of the abstract conclude: 
BOVen is well tolerated and achieves rapid uMRD: 70% PB-uMRD and 62% BM-uMRD with limited follow-up (to be updated on presentation). Fifteen (41%) had confirmation of the prespecified uMRD endpoint and are in follow-up off therapy per protocol. The value of MRD-directed treatment duration will be evaluated with continued follow up.
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John C. Byrd, Jennifer A. Woyach, Richard R. Furman, et al.
 
The authors of the abstract conclude: 
Long-term data from ACE-CL-001 in patients with TN CLL/SLL further support the favorable results with acalabrutinib in phase 3 studies and demonstrate durable responses with no new long-term safety issues.
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Andy Rawstron, Nichola Webster, Surita Dalal, et al.
 
The authors of the abstract conclude: 
The initial rate of disease depletion (during the first two months of combined IBR+VEN exposure) is highly predictive of longer-term response to combination IBR+VEN treatment in relapsed/refractory CLL. Patients who do not show rapid disease clearance and have persistent MRD after 12 months of combination IBR+VEN usually have stable or slowly decreasing disease levels typically seen in IBR monotherapy. MRD levels remain undetectable or low in the majority of patients more than one year after stopping treatment. 
 
Startseite Kongressberichte & Archiv Virtual Edition of the 25th Annual Congress of the European Hematology Association Oral Sessions Chronic Myeloid Neoplasms MDS: MDS:

Novel treatments for MDS II

MBG453 combined with Dec or Aza was safe and well tolerated in pts with HR-MDS and AML, with the most common TEAEs consistent with that for single-agent HMA. Both combinations showed antileukemic activity with encouraging response rates and emerging durability, supporting further development of MBG453 combined with HMAs in MDS/AML. (A Brunner & AH Wei contributed equally) 
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Nico Gagelmann, Anita Badbaran, Rashit Bogdanov, et al.
 
The authors of the abstract conclude: 
This proposed model incorporates genetic and clinical information being the first that was developed and externally validated specifically in CMML undergoing HCT. Furthermore, the model suggests improved prognostic ability for post-HCT outcome and significantly reclassifies patients' individual risk. Therefore, this model may facilitate personalized counseling and treatment stratification.
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Sallman David, Monzr Al Malki, Adam Asch, et al.
 
The authors of the abstract conclude: 
Magrolimab is a novel macrophage targeting immunotherapy that with AZA is well tolerated with durable efficacy in MDS.  A potential registration single arm MDS cohort is ongoing (NCT03248479).  ENHANCE, a randomized Ph3 MDS trial of magrolimab + AZA vs. AZA is being initiated. Additional patients, follow up and translational analyses will be reported at time of presentation. Funded by Forty Seven and the California Institute for Regenerative Medicine
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Amer M. Zeidan*1, Daniel A. Pollyea2, Jacqueline S. Garcia, et al. 
 
The authors of the abstract conclude: 
Ven+Aza combination therapy was well tolerated in pts with RR-MDS and the AEs were manageable. The CR+mCR of 40% and estimated 12-month OS of 65% with Ven+Aza is encouraging. Updated analyses on safety, efficacy, genetic alterations, and BCL-2 family member expression with outcomes will be presented.
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Jacqueline S. Garcia, Andrew H. Wei, Uma Borate, et al.
 
The authors of the abstract conclude: 
This preliminary analysis shows promising efficacy of Ven+Aza combination treatment across all IPSS-R cytogenetic risk categories, and suggests prognostic relevance of the IPSS-R cytogenetic scoring system. Further analyses evaluating the association of genetic alterations and BCL-2 family member expression on efficacy outcomes will be presented.

 

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