CLL AND MORE

A. Tedeschi, Milan (Italy, et al.

FIVE-YEAR FOLLOW-UP OF FIRST-LINE IBRUTINIB FOR TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA//SMALL LYMPHOCYTIC LYMPHOMA

Authors Conclusion from the abstractSingle‐agent ibr sustained superior PFS and OS compared to chl, including for pts with high‐risk genomic features, in the longest follow‐up to date from a phase 3 study of first‐line BTK‐directed therapy. After up to 66 mo follow‐up, responses to ibr improved over time with almost three‐fold more pts achieving CR/CRi with long‐term follow‐up. More than half of pts remain on long‐term continuous ibr treatment, and no new safety signals emerged.

 

O. Al-Sawaf, Cologne (Germany), et al.

HIGH EFFICACY OF VENETOCLAX PLUS OBINUTUZUMAB IN PATIENTS WITH COMPLEX KARYOTYPE (CKT) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A PROSPECTIVE ANALYSIS FROM THE CLL14 TRIAL

Authors Conclusion from the abstractCKT, which can be observed frequently in older, treatment‐naïve CLL pts, correlates with CLL‐IPI high/very high risk, although 2/3 of these pts do not show TP53aberrations. CKT is associated with shorter PFS and OS in pts treated with ClbG, including pts without TP53 aberrations. VenG can overcome this adverse risk. These data support the importance of chromosome analysis before frontline therapy, and the value of VenG in CLL CKT pts.

 

J. Wu, San Francisco, CA (USA), et al. 

IMPACT OF MAJOR GENOMIC ALTERATIONS ON OUTCOME OF RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS RECEIVING VENETOCLAX PLUS RITUXIMAB IN THE PHASE 3 MURANO STUDY

Authors Conclusion from the abstractWe assessed the mutational landscape of R/R CLL by WES and confirmed prior mutation frequency reports. Superior PFS benefit was observed for VenR vs BR in all clinical and molecular subgroups assessed, including the key CLL driver mutations reported here. NOTCH1 mutations may define a new high‐risk pt subgroup for VenR. To address the biological basis of the findings, MVA, further validation in larger cohorts and deep sequencing for subclones are needed.

 

S. Handunnetti, Melbourne (Australia), et al.

AN UNDETECTABLE PB MRD STATUS SHOULD BE THE THERAPEUTIC GOAL WITH VENETOCLAX THERAPY IN RELAPSED/ REFRACTORY CLL

Authors Conclusion from the abstractPB uMRD commonly correlates with BM uMRD in CLL patients treated with Ven, and serves as an equivalent predictor of long term outcome. Patients who have not achieved PB uMRD by 24 months are unlikely to do so. This group is enriched for TP53dysfunction and complex karyotype. While patients achieving uMRD have prolonged TTP, CLL eventually recrudesces, supporting a drive to time‐limited combination therapy.

 

T. Siddiqi, Duarte, CA (USA, et al.

TRANSCEND CLL 004: MINIMAL RESIDUAL DISEASE AFTER LISOCABTAGENE MARALEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA

Authors Conclusion from the abstractIn this study of heavily pretreated patients with standard‐ and high‐risk CLL/SLL and previous ibrutinib treatment, liso‐cel–related toxicities of CRS and NE were manageable and grade 3 or higher events were limited. Patients rapidly achieved CR/CRi and undetectable MRD. The phase 2 component of the study is currently enrolling patients for treatment at dose level 2. Additional follow‐up will be presented.

 

Tiacci, Perugia (Italy), et al. 

THE BRAF INHIBITOR VEMURAFENIB PLUS RITUXIMAB PRODUCES A HIGH RATE OF DEEP AND DURABLE RESPONSES IN RELAPSED/REFRACTORY HAIRY CELL LEUKEMIA: UPDATED RESULTS OF A PHASE-2 TRIAL E. 

Authors Conclusion from the abstract: Vemurafenib plus rituximab is a brief, safe and non‐myelotoxic regimen inducing MRD‐negative durable responses in most relapsed/refractory HCL patients. Randomized testing against the chemotherapy‐based standard of care in the frontline setting is warranted.