The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

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

May 19, 2017

On 15 thMay 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 Gelderfrom 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.

Patient and disease characteristics

Risk factor

Numbers

Age (years)

 

<45 years

80 (41%)

45–50 years

117 (59%)

Median

46 years

Prior Chemosensitivity

 

Purine-analogue refractory

67 (40%)

Relapse after chemo-immunotherapy

32 (19%)

Cytogenetics

 

Del(17p)

23 (17%)

Del(11q) and no del(17p)

48 (35%)

Median number of prior lines of therapy (range)

3 (0–10)

Previous autologous HCT

24 (12%)

Responsiveness at time of alloHCT

114 (62%)

Karnofsky (n=179)

 

90–100

152 (84%)

≤80

29 (16%)

Transplant characteristics

Risk factor

Numbers

Conditioning (n=194)

 

Non-myeloablative (2Gy TBI-based)

58 (30%)

Reduced intensity

89 (46%)

Myeloablative

47 (24%)

Donor type

 

Matched related

83 (42%)

Match unrelated

97 (49%)

Partially mismatched unrelated

17 (9%)

Patient-donor sex match (n=193)

 

Female donor for male patient

39 (20%)

CMV IgG in patient (n=180)

 

Positive

69 (38%)

2-year NRM risk factor – multivariate analysis

Risk factor

HR (95% CI)

p-value

Age (in decades)

0.8 (0.4–1.6)

0.55

Cytogenetics

 

 

No del(17p) or del(11q)

1

 

Del(17p) and/or del(11q)

1.3 (0.6–2.9)

0.51

Donor type

 

 

HLA-identical sibling

1

 

Matched unrelated

2.5 (1.1–5.4)

0.03

Partially matched unrelated

4.0 (1.4–11.6)

0.01

Sex match

 

 

All other combination

1

 

Female donor for male patient

1.5 (0.7–3.3)

0.27

8-year PFS risk factor – multivariate analysis; patient characteristics

Risk factor

HR (95% CI)

p-value

Donor type

 

 

HLA-identical sibling

1

 

Matched unrelated

1.2 (0.8–1.8)

0.41

Partially matched unrelated

2.8 (1.5–5.2)

<0.01

Sex match

 

 

All other combination

1

 

Female donor for male patient

1.2 (0.7–1.9)

0.50

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

Defining good and poor transplantation risk patients

Good risk patients

Poor risk patients

46 years old

Del(17p) and/or del(11q)

No prior autoHCT

Remission at the time of alloHCT

No remission at the time of alloHCT

HLA-matched sibling

 

No sex mismatch

Unrelated female donor

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%.

  1. van Gelder M.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. XVII International Workshop on Chronic Lymphocytic Leukemia; 2017 May 12–15; New York, USA.