iwCLL 2017 | Allogeneic transplantation using HLA-compatible donors is effective in younger high-risk CLL patients - an EBMT registry study

On 15^th May 2017, during iwCLL, the second half of the “Additional Therapies for the Relapsed/Refractory CLL Patient” session was jointly chaired by Guillermo Dighiero (Unité d'Immunohématologie et d'Immmunopathologie, Institut Pasteur) and Federico Caligaris-Cappio (Università Vita-Salute San Raffaele).

During this session, Michael van Gelder from Maastricht University Medical Center, The Netherlands, gave a presentation titled “Allogeneic hematopoietic stem cell transplantation using HLA-compatible donors in younger high cytogenetic risk CLL patients results in very high long-term Progression-Free Survival and Low Non-Relapse Mortality and may therefore favorably compete with the sequential use of kinase- and BCL2 inhibitors – a report From the CMWP of EBMT.”

Current preferred treatment option for R/R CLL include:

• Kinase inhibitors: ibrutinib, idelalisib+rituximab
• BCL2 inhibitors: venetoclax

These achieve very high responses; however, relapses remain especially in high-risk CLL:

• Del(17p), TP53 mutation or del(11q) (median PFS with ibrutinib is 26 months)
• Up to 33% progress with Richter’s transformation

High-risk CLL patients generally respond to kinase and BCL2 inhibitors, either immediately or after failure on ≥1 kinase and/or BCL2 inhibitors. Short PFS has been reported after sequential use of kinase and/or BCL2 inhibitors.

Allogeneic Hematopoietic Stem Cell Transplant (alloHCT) can result in very long PFS, independent of cytogenetics. But, Non-Relapse Mortality (NRM) is a downside; it depends on age, performance, remission status at time of alloHCT, HLA match and donor-patient relation, sex-mismatch, etc.

EBMT registry data of transplanted CLL patients was analyzed and focused on younger (<50 years old) high-risk CLL patients and aimed to identify factors that predict low 2-year NRM and high 8-year PFS. It also aimed to study the impact of del(17p)/del(11q) on PFS. Median follow-up was 90.4 months.

Using the Cox models for 2- and 8-year PFS:

In conclusion, low-NRM risk factors can be identified (good transplant risk). Good transplant risk young CLL patients have a fairly good outcome: very low NRM and 8-year PFS of more than 50%.