iwCLL 2017 | Final results of the phase II ICLL03 RICAC-PMM trial of RIC allo-SCT for high-risk patients 

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).

Olivier Tournilhac, MD, PhD, from CHU Estaing, Clermont-Ferrand, France, gave a talk titled “RIC allogeneic stem cell transplantation for high risk CLL followed by pre-emptive MRD-based immune intervention. Phase II ICLL03 RICAC-PMM trial: final results” during this session.

The ICLL003 RICAC-PMM study (NCT01849939) is a multicenter, phase II study by the FILO and SFGM-TC groups, and aimed to increase the rate of MRD-negativity at 12 months post-ASCT using a pre-emptive, MRD based, immune intervention algorithm. MRD-negativity was assessed by 10 color flow cytometry, and was defined as <0.01% (10^-4) in blood and bone marrow. Between September 2012 and February 2015, 43 patients were included from 16 centers in France; 42 patients were included in the analysis (1 patient had no ASCT, due to donor comorbidities).

At transplantation:

• Median age = 58 years (range, 40–68)
• Time from diagnosis to transplant = 4.4 years (range, 0.2–14.7)
• Median number of prior therapies = 2 (range, 1–5) including at last line: alemtuzumab (n=17), immunochemotherapy (n=21), and BCR inhibitor (n=4)
• Response: PR = 78%; CR/CRi = 22%
• Pre-ASCT MRD = 0.78% (0.005–70) and undetectable in 6 patients
• Allogeneic transplantation per the EBMT 2007 criteria

*including 1 patient with complex karyotype but 17p deletion, eventually ruled out (TP53 wild type)
Del(17p) first-line*	11 (26%)
Del(17p) R/R	16 (38%)
Relapse <2 years, following fludarabine combination and no del(17p)	15 (36%)

A: M0 MRD(-); B: M0 MRD (+), no need of immune intervention; C: M0 MRD(=), immune intervention - CSA withdrawal; D: M0 MRD(+), immune intervention – CSA withdrawal and DLI

At 24 months:

• Follow-up = 36 months (19–53)
• PFS = 66.7% (95% CI, 51.5–79.0%)
• OS = 90.5% (95% CI, 77.9–96.2%)
• NRM = 7.1% (95% CI, 3.1–11.1%)
• 7 deaths reported, 4 due to toxicity and 3 due to Richter syndrome

In terms of safety:

• aGvHD ≥Grade 2 in 26% of patients; Grade 3 in 10%
• Limited cGvHD in 38% of patients (95% CI, 23–53); Extensive cGvHD in 23% of patients (95% CI, 10–36)
  • Including cGvHD in 2 patients following immune intervention (n=1 DLI, n=1 CSA withdrawal)
• 4 toxic deaths reported (CMV/EBV in month 1, GvHD in months 6 and 10, and pulmonary aspergillosis/pneumocystosis infection in month 9)

Olivier Tournilhac concluded his talk with a concise summary slide: