Note: A hodgepodge of trials, added to as I come across them at work, during teaching or whilst preparing pages for this site. Interpretation of trial results is opinion (my own or my teachers’) and is included only as a prompt to read further and not as gospel.
chronic lymphocytic leukaemia
FCR x6 vs R-Benda x6
FCR superior for ORR, MRD-neg remissions, length of first remission in young, fit patients
FCR arm had more serious adverse events
Overall survival similar for both arms
Chlorambucil-Obinutuzumab vs Chlorambucil-Rituximab vs Chlormabucil alone
Chlorambucil-Obinutuzumab had superior PFS and TTNT
Infusion reactions more common with obinutuzumab
Chlorambucil-Ofatunumab vs Chlormabucil alone
Combo better PFS but no difference in OS
Hard to compare to CLL11 as different dose of chlorambucil used
CML - stopping tki's
821 patients on 1st line imatinib or after IFN, dasatinib or nilotinib at 1st or more line, excluding patients with prior resistance
Minimum 3 years Rx, with minimum 1 year in MR4
Trial outcome suggests best prognosis is min. 6 yrs treatment, 3yrs in MR4
Definition of molecular relapse was loss of MMR – 45% of patients by 18 months
For patients in MR4
Reduced dose for 12 months, and then stopped if patient had not lost MMR
Reducing dose is safe (may help with SE’s)
If you stop after prior dose reduction, better chance of staying in MR4 (vs EUROSKI)
219 patients. Phase 2 randomised trial for 1st treatment of primary CNS lymhpoma
HD-MTX + Cytarabine vs additional Rituximab vs additional Rituximab and Thiotepa (MATRix)
Followed by Whole Brain Radiotherapy vs High Dose Autograft
CR of 23%, 30% and 49% respectively for the induction regimens given above
69% 2 year OS
6% treatment-related mortality (TRM)
diffuse large b cell lymphoma
GOYA Study 2017
1400 patients, previously untreated advanced-stage DLBCL
R-CHOP vs G-CHOP (G = Obinutuzumab)
No difference in 3-yr PFS (70 vs 67%). Grade 3-5 sdverse events higher for G-CHOP
Later retrospective analysis also concludes no benefit for 8x R-CHOP over 6x R-CHOP
StiL Study 2013
R-Benda vs R-CHOP for previously untreated FL
PFS better with R-Benda. No OS difference.
PRIMA Trial 2011
Randomised, open label, 1200 patients
2 years R-maintenance vs observation only post local first line standard of care chemo
10 year update released – 10-yr PFS 51% with, 35% without. No OS difference at 10 years
GALLIUM Study 2017
Obinutuzumab-Chemo vs Rituximab-Chemo for previously untreated FL
Improves PFS. No OS difference
RELEVANCE Trial 2018
Phase 3, 1000 patients
Rituximab-Lenalidomide (R2) for 18 cycles vs R-Chemo for advanced, previously untreated FL
Both arms received R-maintenance.
Negative trial. Designed as superiority trial and did not meet this.
Non-significant higher CR and PFS for R-Chemo
mantle cell lymphoma
Alternating cycles of R-Maxi-CHOP and High dose cytarabine for 6 cycles, followed by autograft
5-year EFS >60%
2016 update: No plateau in the survival curve, with ongoing late relapse events
2016 update: 40% of low and intermediate risk patients still in 1st remission at 12 years
299 patients, R-DHAPx4, followed by BEAM Autograft (R-CHOPx4 given is not in CR/PR post DHAP)
The R-DHAP could be with cisplatin or oxalaplatin
Post autograft, randomised to rituximab maintenance or not
4-year OS 78%, PFS 67% and superior in the R-maintenance arm
Myeloma XI Trial (ASH 2018, publication awaited)
1274 patients. High and Low intensity arms
Carfilzomib/Cyclo/Len/Dex (KCRD) v.s. Cyclo/Len/Dex (CRD) vs CTD
CTD & CRD get VCD if poor response
Followed by Autograft
Randomised to maintenance or no maintenance
KCRD higher rates of VGPR or better, and higher rate of MRD negativity (77%) post autograft, which translates to a 2 year PFS advantage over CRD.
CTD v.s. Cyclo/Len/Dex
VCD if poor response
Randomised to Len maintenance, Len/Vorinostat maintenance or no maintenance
Subsequent analysis of early relapse patients
14% of patients progressed within 12 months. This group has a 3-yr OS 28% compared to 53% for those with remission >12 months.
More likely to be in early relapse group if any of the following at diagnosis: Lambda LC, higher marrow PC %, anaemia or stage 3 ISS.
33% of early relapse group had 1 high risk genetic abnormality, 31% ³2.
i.e. 1/3 had standard risk genetics à more to be learnt about risk assessment.
Myeloma XII Trial (ACCoRD)
Opening soon, three questions:
1. Ixazomib / Thal /Dex (ITD) v.s. VTD
2. Autograft vs Autograft + Ixazomib
3. ITDx2 consolidation vs Ixazomib maintenance
Ixazomib/Lenalidomide/Dex vs Placebo/Len/Dex
722 R/R patients with 1-3 prior lines of therapy
Improved PFS, 20 months vs 14 months
Median overall survival not reached, i.e. survival benefit not demonstrated yet
SE: Thrombocytopenia, rash, diarrhoea
CDF approved Jan 2018 as 3rd or 4th line treatment, provided not refractory to Bortez
MAIA Study (ASH 2018, publication awaited)
Phase 3. Daratunumab-Lenalidomide (D-Rd) vs Rd mono in transplant-ineligible newly diagnosed myeloma.
30 month PFS 71% vs 56%
MRD negativity 24% vs 7%
?New first choice treatment for older patients (outside UK)
Phase 3, placebo controlled. >650 patients.
Ixazomib maintenance vs placebo post-autograft. 2 years treatment then stop.
39% improvement in PFS, 6 month increase in PFS. Also of benefit in MRD-neg patients.
No OS data yet
RESPONSE Trial 2015
222 patients venesection dependent, splenomegaly and HU intolerant or resistant
Complex study, hard to enroll, confounding factors
Lead to Ruxolitinib license for PV resistant/intolerant to HU
5-yr update: Ruxolitinib is immunosuppressive, suggestion of increased rates of 2nd cancers
RELIEF Trial 2014
Ruxolitinib for symptom relief in PV. No better than HU.
600 patients, Phase 3, placebo-controlled
Brentuximab + CHP (A-CHP) vs CHOP
Most patients had anaplastic large cell lymphoma (but any CD30+ peripheral T-cell eligible)
Median PFS 48 months for A-CHP vs 20 months for CHOP