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

CLL10 2013

  • 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

CLL11 2014

  • Chlorambucil-Obinutuzumab vs Chlorambucil-Rituximab vs Chlormabucil alone

  • Chlorambucil-Obinutuzumab had superior PFS and TTNT

  • Infusion reactions more common with obinutuzumab

COMPLEMENT-1 2015

  • 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

 

EURO-SKI 2016

  • 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

 

DESTINY 2017

  • For patients in MR4

  • Reduced dose for 12 months, and then stopped if patient had not lost MMR

  • Conclusions:

    • Reducing dose is safe (may help with SE’s)

    • If you stop after prior dose reduction, better chance of staying in MR4 (vs EUROSKI)

cns lymphoma

IELSG32 2016

  • 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

follicular

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

 

NORDIC MCL2 STUDY 2008

  • 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

 

LyMa TRIAL 2017

  • 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

Myeloma XI Trial (ASH 2018, publication awaited)

  • 1274 patients. High and Low intensity arms

  • High intensity

    • 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.

  •  Low intensity

    • 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

 

Tourmaline-MM1 Trial 2016

  • 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)

Tourmaline-MM3 2018

  • 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

polycythaemia

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.

T-CEll lymphoma

ECHELON-2 2018

  • 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

  • OS advantage