Trials · Topics · Leukemias

Leukemias clinical trials

120 Leukemias trials (Malignant Hematology) summarized for fellows and board review, newest first within each disease. Each summary covers design, results, toxicity and what changed in practice.

Jump to: CLL · AML · ALL · MDS · CML · HCL

CLL (34)

• BRUIN CLL-322 trial Lancet 2026
  Adding pirtobrutinib to fixed-duration venetoclax-rituximab significantly improved PFS versus VR in relapsed/refractory CLL/SLL, with benefit preserved in patients...
• CLL6 RESIDUUM final analysis Br J Haematol 2026
  In CLL patients with residual disease after first-line FCR chemoimmunotherapy, 2 years of lenalidomide maintenance significantly prolonged PFS (64.6 vs 42.4 months...
• CRISTALLO trial Blood 2026
  Fixed-duration VenO achieved markedly deeper MRD responses than FCR/BR in fit untreated CLL, confirming and extending GAIA-CLL13. Further evidence that...
• AMPLIFY NEJM 2025
  Fixed-duration AVO and AV significantly prolonged PFS compared to chemoimmunotherapy in treatment-naive CLL, with markedly higher uMRD rates and particular benefit in...
• BRUIN CLL-313 JCO 2025
  Pirtobrutinib demonstrated superior PFS over BendaR in treatment-naive CLL/SLL, with a substantially more favorable tolerability profile. OS trends favored...
• BRUIN CLL-321 JCO 2025
  Pirtobrutinib significantly improved PFS versus idelalisib + rituximab or BR in BTKi-pretreated R/R CLL/SLL (HR 0.54), with higher ORR and a superior safety profile...
• CLL17 NEJM 2025
  Fixed-duration VenO and VenI achieved 3-year PFS non-inferior to continuous ibrutinib in treatment-naive CLL, with significantly higher uMRD rates (~57% and 53% vs...
• BRUIN (Richter transformation) Lancet Haematol 2024
  Pirtobrutinib achieved a 50% ORR in BTKi-pretreated Richter transformation - a notable response rate in this historically treatment-refractory population. An mOS of...
• FELIX NEJM 2024
  Obe-cel achieved 76.6% CR/CRp with 97% MRD-negativity in heavily pretreated adult R/R B-ALL, with a markedly improved safety profile vs brexucabtagene autoleucel...
• FLAIR NEJM 2024
  Ibrutinib-based frontline therapy (IR and ibrutinib monotherapy) significantly improved PFS and OS versus FCR in treatment-naive CLL, with particularly large benefit...
• ALPINE NEJM 2023
  Zanubrutinib demonstrated superior ORR and significantly improved 2-year PFS (HR 0.65) versus ibrutinib in R/R CLL/SLL, with significantly less atrial fibrillation...
• BRUIN (phase 1/2) NEJM 2023
  Pirtobrutinib achieved a 73% ORR in heavily pretreated BTKi-pretreated CLL/SLL, including patients with C481S BTK mutations, with a favorable safety profile - notably...
• CLL13 (GAIA) NEJM 2023
  In fit treatment-naive CLL, VenObi and VenIbr significantly improved uMRD rates and PFS over CIT, with the triplet VenIbr achieving the highest uMRD (92.2%). VenObi...
• TRANSCEND CLL 004 Lancet 2023
  Liso-cel achieved a 20% CR/CRi rate and high uMRD rates (63% peripheral blood) in heavily pretreated R/R CLL/SLL, with impressive activity in Richter transformation...
• CAPTIVATE Blood 2022
  Fixed-duration ibrutinib + venetoclax (12 months) achieved high uMRD rates (56% in peripheral blood) and durable responses in treatment-naive CLL, with 88% 3-year PFS...
• GLOW NEJM Evid 2022
  Ibrutinib-venetoclax fixed-duration achieved dramatically superior uMRD (84.5% vs 29.3%) and PFS over Clb+G in older/unfit treatment-naive CLL, with the practical...
• SEQUOIA Lancet Oncol 2022
  Zanubrutinib demonstrated significantly superior PFS over BR in treatment-naive CLL, with a 5-year PFS HR of 0.29 and sustained benefit. The low AFib rate (7.1% at 5...
• ELEVATE-RR JCO 2021
  Acalabrutinib demonstrated non-inferior PFS to ibrutinib in R/R CLL with del(17p) and/or del(11q), with significantly lower rates of atrial fibrillation (9.4% vs...
• Ascend Trial, Acala vs Idela+R or BR for rrCLL JCO 2020
  Acalabrutinib monotherapy significantly improved PFS over idelalisib+rituximab or bendamustine+rituximab in relapsed/refractory CLL, with a favorable tolerability...
• CLL14 Lancet Oncol 2020
  Fixed-duration venetoclax plus obinutuzumab significantly prolonged PFS (5-yr PFS 35% vs 12%, HR 0.35) and achieved substantially higher MRD-negativity rates versus...
• ELEVATE-TN Lancet 2020
  Both acalabrutinib + obinutuzumab and acalabrutinib monotherapy significantly prolonged 5-year PFS versus chlorambucil-obinutuzumab (HR 0.10 and 0.22, respectively)...
• CLL 14 trial, obi+ven vs obi+chlorambucil NEJM 2019
  Fixed-duration obinutuzumab-venetoclax produced significantly higher PFS and undetectable-MRD rates than obinutuzumab-chlorambucil in untreated CLL, supporting a...
• ECOG E1912 NEJM 2019
  Ibrutinib+rituximab demonstrated significantly superior PFS and, notably, a meaningful OS benefit compared with FCR in young, fit treatment-naive CLL patients without...
• iLLUMINATE Lancet Oncol 2019
  Ibrutinib + obinutuzumab demonstrated markedly superior PFS over Clb + obinutuzumab in treatment-naive CLL of all ages, with a hazard ratio of 0.23. This established...
• Alliance A041202 NEJM 2018
  Ibrutinib regimens significantly improved PFS over BR in elderly treatment-naive CLL. Adding rituximab to ibrutinib did not improve PFS, ORR, or OS over ibrutinib...
• MURANO NEJM 2018
  Fixed-duration venetoclax plus rituximab (24 months total) achieved dramatically superior 5-year PFS (38% vs 5%, HR 0.19) and significantly improved OS (HR 0.40)...
• CLL10 Lancet Oncol 2016
  FCR showed superior PFS over BR in fit treatment-naive CLL, but with significantly higher hematologic toxicity and infection rates and no OS benefit. BR offers an...
• HELIOS Lancet Oncol 2016
  Ibrutinib added to bendamustine-rituximab significantly improved PFS in R/R CLL/SLL versus placebo-BR (HR 0.203), with benefit across all prespecified subgroups...
• COMPLEMENT-1 Lancet 2015
  Ofatumumab + chlorambucil significantly improved PFS and ORR compared with chlorambucil alone in fit-for-chlorambucil treatment-naive CLL. No OS benefit was...
• RESONATE-2 NEJM 2015
  Ibrutinib demonstrated dramatically superior PFS over chlorambucil in elderly CLL, with a 10-year median PFS of 8.9 years - the longest reported continuous BTK...
• CLL 11 trial, chlorambucil wt/wo CD-20i NEJM 2014
  Adding an anti-CD20 antibody (obinutuzumab or rituximab) to chlorambucil improved PFS in untreated CLL with comorbidities; obinutuzumab-chlorambucil was superior to...
• RESONATE trial, Ibrutinib vs Ofa in rrCLL NEJM 2014
  Ibrutinib was superior to ofatumumab in PFS, OS, and response in relapsed/refractory CLL/SLL, including high-risk del(17p) disease.
• Alemtuzumab in T-PLL Blood 2011
  Alemtuzumab achieved a 76% ORR and 39% CR rate in T-PLL - far superior to historical CHOP-based chemotherapy - and improved median OS to 21 months. Allogeneic SCT in...
• CLL8 Lancet 2010
  FCR significantly improved PFS, CR rates, and MRD negativity compared with FC in treatment-naive CLL, and a subsequent long-term analysis demonstrated an OS benefit....

AML (30)

• AAML1831 J Clin Oncol 2026
  CPX-351 induction was inferior to standard daunorubicin/cytarabine in de novo pediatric AML, and the randomization was closed early for futility. The EFS difference...
• DASATINIB IN CBF-AML Blood 2026
  Adding dasatinib to intensive chemotherapy did not improve EFS, OS, or relapse-free survival in CBF-AML, including in patients with KIT mutations, and was associated...
• LACEWING trial Haematologica 2026
  Gilteritinib plus azacitidine roughly doubled the response rate versus azacitidine alone (70.2% vs 36.8%) but did not translate into an overall survival benefit (9.82...
• PARADIGM trial N Engl J Med 2026
  In induction-eligible AML, azacitidine-venetoclax significantly prolonged EFS versus intensive induction chemotherapy, with fewer grade ≥3 infections and hemorrhages....
• AML17/AML19 Lancet Haematol 2025
  Sequential molecular MRD monitoring did not improve overall survival in the overall population of younger adults with AML (HR 1.11, P=.25) - a negative result for the...
• Olutasidenib (phase 2 pivotal) J Hematol Oncol 2025
  Olutasidenib achieved a 35% CR/CRh rate (ORR 48%) in heavily pretreated IDH1-mutated R/R AML, with a median response duration of 25.3 months - supporting durable...
• AUGMENT-101 JCO 2025
  Revumenib achieved a 63% ORR and 30% CR+CRh rate with MRD negativity in 53% of responders in heavily pretreated R/R KMT2A-rearranged and NPM1-mutant acute leukemia...
• KOMET-001 Lancet Oncol 2024
  Ziftomenib 600 mg QD (RP2D) achieved a 35% CR rate in NPM1-mutated R/R AML, supporting a meaningful single-agent response in a heavily pretreated population....
• IDHENTIFY Blood 2023
  IDHENTIFY did not demonstrate an OS advantage for enasidenib over CCR in R/R IDH2-mutated AML (mOS 8.8 vs 9.6 months, HR 1.06), despite statistically higher CR (27%...
• QuANTUM-First Lancet 2023
  Quizartinib added to standard induction, consolidation, and maintenance chemotherapy significantly improved OS in newly diagnosed FLT3-ITD+ AML (HR 0.78, mOS 31.9 vs...
• AGILE NEJM 2022
  Ivosidenib + azacitidine significantly improved OS (24.0 vs 7.9 months, HR 0.44) and CR rates (47.2% vs 14.9%) in newly diagnosed IDH1-mutated AML ineligible for...
• Treosulfan/Flu (EBMT) Br J Haematol 2021
  Treosulfan/fludarabine demonstrated GRFS and OS numerically superior to both MAC and RIC in this large EBMT registry analysis, with lower NRM than MAC and lower...
• QUAZAR trial, Aza maintenance NEJM 2020
  Oral azacitidine maintenance significantly prolonged OS and RFS in older HSCT-ineligible AML patients in first remission after intensive chemotherapy.
• VIALE-A NEJM 2020
  Venetoclax plus azacitidine significantly improved OS (14.7 vs 9.6 months, HR 0.66) and achieved dramatically higher composite remission rates (66% vs 28%) versus...
• VIALE-C Blood 2020
  Venetoclax + LDAC significantly improved CR+CRi rates (48% vs 13%) but did not meet its primary endpoint of OS superiority (mOS 7.2 vs 4.1 months, HR 0.75, P=.11) in...
• ADMIRAL trial, gilteritinib in rrAML FLT3-ITD NEJM 2019
  Gilteritinib provided a significant OS benefit over salvage chemotherapy in relapsed/refractory FLT3-mutated AML, with higher remission rates and favorable tolerability.
• BRIGHT AML 1003 Leukemia 2019
  Glasdegib + LDAC demonstrated a statistically significant OS improvement over LDAC alone (mOS 8.8 vs 4.9 months, HR 0.46, P=.0002) with higher CR rates (17% vs 2%)...
• QuANTUM-R Lancet Oncol 2019
  Quizartinib significantly improved OS versus salvage chemotherapy in R/R FLT3-ITD AML (HR 0.76, P=.02), with higher composite remission rates (48% vs 27%) and greater...
• CPX-351 in sAML JCO 2018
  CPX-351 significantly improved median OS and remission rate versus 7+3 in patients 60-75 years with newly diagnosed secondary AML (t-AML/AML-MRC).
• Ivosidenib R/R AML (phase 1/2) NEJM 2018
  Ivosidenib achieved a 32.2% CR+CRh rate and 41.6% ORR in R/R IDH1-mutated AML with an mOS of 8.8 months - a clinically meaningful response in a heavily pretreated...
• RELAZA-2 Lancet Oncol 2018
  Preemptive azacitidine in MRD-positive AML/MDS patients in morphological remission met its primary endpoint - 58% relapse-free and alive at 6 months, exceeding the...
• BMT CTN 0901 JCO 2017
  MAC provided significantly superior OS and lower relapse vs RIC in fit AML/MDS patients, driven by dramatically lower relapse (44.9% vs 65.3%). NRM did not differ...
• Enasidenib R/R AML (phase 1/2) Blood 2017
  Enasidenib achieved a 30.7% CR+CRh rate and 40.3% ORR in heavily pretreated R/R IDH2-mutated AML, supporting FDA accelerated approval. The characteristic class...
• RATIFY/CALGB 10603 trial NEJM 2017
  Adding midostaurin to standard chemotherapy and as maintenance reduced the risk of death by 22% in younger adults with FLT3-mutated AML, establishing FLT3 inhibition...
• APML4 Lancet Haematol 2015
  Adding ATO to ATRA + idarubicin in both induction and consolidation produced excellent long-term outcomes with markedly reduced relapse risk vs historical controls...
• AZA-AML-001 Blood 2015
  Azacitidine did not significantly improve overall survival vs conventional care regimens in elderly unfit AML (HR 0.85, P=.1009), failing to meet the primary...
• APL0406 Lo-Coco Trial, ATRA+ATO NEJM 2013
  ATRA+ATO was non-inferior (and on update superior) to ATRA+chemotherapy in newly diagnosed low/intermediate-risk APL, with substantially less hematologic toxicity...
• ALFA-0701 Lancet 2012
  Fractionated gemtuzumab ozogamicin added to standard 7+3 significantly improved EFS (17.1 vs 9.7 months) and RFS in newly diagnosed AML age 50-70, with particular...
• ECOG1900 trial NEJM 2009
  Intensified induction with high-dose daunorubicin (90mg/m2) significantly improved complete remission and overall survival in younger AML patients, particularly those...
• Post Remission Cytarabine Trial NEJM 1994
  A significant cytarabine dose-response was demonstrated for post-remission therapy in AML; high-dose cytarabine (3 g/m2) improved DFS and OS versus lower doses...

ALL (20)

• GIMEMA LAL2317 Blood 2025
  Sequential insertion of blinatumomab into a standard GIMEMA chemotherapy backbone substantially increased MRD negativity (72% → 93%), with 73% of MRD-positive...
• GRAALL-2014 Blood 2025
  GRAALL-2014 demonstrated that age-adapted chemotherapy intensity and MRD-guided transplant restriction significantly improved OS in adults with Ph-negative ALL...
• AALL1731 NEJM 2024
  Adding two 28-day blinatumomab cycles to standard chemotherapy improved 3-year DFS from 87.9% to 96.0% (HR 0.39, P<.0001) in children and young adults with NCI...
• ECOG E1910 NEJM 2024
  Adding blinatumomab to consolidation chemotherapy in MRD-negative BCR::ABL1-negative adult B-ALL improved 3-year OS from 68% to 85% (HR 0.41, P=.003) - a 17...
• PhALLCON JAMA 2024
  Ponatinib + reduced-intensity chemotherapy produced a significantly higher MRD-negative CR rate at end of induction than imatinib (34% vs 17%), establishing ponatinib...
• Mini-hyperCVD + Inotuzumab (older adult ALL) Lancet Haematol 2023
  Mini-hyper-CVD + inotuzumab ozogamicin achieved 98% CR/CRi with 82% MRD-negativity in patients ≥60 years with newly diagnosed Ph-negative B-ALL - markedly superior to...
• ZUMA-3 Lancet 2021
  Brexucabtagene autoleucel achieved 71% CR/CRi in adult R/R B-ALL with 97% MRD-negativity among responders. With mOS of 25.4 months in a population that historically...
• AALL0434 JCO 2020
  Adding nelarabine to the Augmented BFM backbone with HD-MTX significantly improved 4-year DFS (86% vs 78%) in pediatric/young adult T-ALL without increased toxicity....
• D-ALBA (GIMEMA LAL2116) NEJM 2020
  Dasatinib + blinatumomab without cytotoxic chemotherapy achieved 98% CR, 60% molecular response after 2 blinatumomab cycles, and 75.8% 53-month OS, with zero...
• CALGB 10403 Blood 2019
  A pediatric-inspired ALL regimen achieved a 3-year EFS of 59% and OS of 73% in AYA patients aged 17-39 with newly diagnosed Ph-negative ALL, substantially exceeding...
• BLAST Blood 2018
  Blinatumomab eradicated MRD in 78% of adults with MRD-positive BCP-ALL in CR. MRD response was strongly associated with prolonged RFS (23.6 vs 5.7 months) and OS...
• ELIANA NEJM 2018
  Tisagenlecleucel achieved 81% remission in pediatric/young adult R/R ALL with 100% MRD-negativity among responders. With 3-year EFS of 44% and mOS not reached, this...
• GRAALL-2003/2005 JCO 2018
  GRAALL-2003/2005 established the pediatric-inspired chemotherapy backbone as effective in adults with Ph-negative ALL (~91% CR, ~58% 5-year OS). Within GRAALL-2005...
• ALCANTARA JCO 2017
  Blinatumomab achieved CR/CRh in 36% of adults with heavily pretreated TKI-resistant Ph+ ALL, including patients with T315I mutations. Responses were deep (88%...
• TOWER, Blinatumab TRIAL NEJM 2017
  Blinatumomab significantly improved OS and CR rate versus standard chemotherapy in relapsed/refractory Ph-negative B-cell precursor ALL, establishing it as standard...
• AALL0232 JCO 2016
  HD-MTX during interim maintenance significantly improved 5-year DFS (91.7% vs 84.2%) in children and young adults with NCI high-risk B-ALL, leading to early trial...
• INO-VATE NEJM 2016
  Inotuzumab ozogamicin achieved a dramatically higher CR/CRi rate (81% vs 29%) and MRD-negativity rate (78% vs 28%) versus salvage chemotherapy in R/R CD22+ B-ALL...
• UKALL 2003 Lancet Oncol 2014
  MRD-guided treatment intensification - augmenting therapy in children/young adults with ≥0.01% MRD at end of induction - significantly improved 5-year EFS (81% vs...
• DA-EPOCH-R (Burkitt) NEJM 2013
  DA-EPOCH-R achieved ~95% freedom from progression and 100% OS in HIV-negative adult Burkitt lymphoma with a short infusion schedule and no prophylactic intrathecal...
• GIMEMA LAL1205 Blood 2011
  Dasatinib + steroid induction achieved 100% CHR in newly diagnosed Ph+ ALL across all ages without cytotoxic chemotherapy - the first demonstration that a TKI-only...

MDS (16)

• ENHANCE J Clin Oncol 2026
  ENHANCE did not meet either primary endpoint: adding magrolimab to azacitidine failed to improve CR or OS in higher-risk MDS and increased severe and fatal toxicity....
• Ivosidenib (IDH1-mutated MDS) Blood Adv 2024
  Ivosidenib demonstrated clinically meaningful activity in R/R IDH1-mutated MDS, with an 83% overall response rate and durable complete remissions (68.6% probability...
• COMMANDS Lancet 2023
  In ESA-naive transfusion-dependent LR-MDS, luspatercept achieved nearly twice the rate of composite transfusion independence plus hemoglobin response compared with...
• Enasidenib (IDH2-mutated MDS) Blood Adv 2023
  Enasidenib demonstrates clinically meaningful activity in IDH2-mutated MDS. Combined with azacitidine it achieved 74% ORR with 70% composite CR in treatment-na ve...
• ENHANCE JCO 2023
  Magrolimab + azacitidine demonstrated promising efficacy in untreated HR-MDS, with a 33% CR rate and 75% ORR including encouraging activity in TP53-mutant disease - a...
• IMerge Lancet 2023
  Imetelstat significantly increased rates of durable transfusion independence versus placebo in heavily pre-treated, ESA-refractory/ineligible LR-MDS, with responses...
• STIMULUS-MDS1 Lancet Haematol 2023
  Neither primary endpoint was met. Sabatolimab added to HMA did not significantly improve CR rates or PFS versus HMA alone in untreated HR-MDS. The HR of 0.75 for PFS...
• IPSS-M NEJM Evid 2022
  The IPSS-M substantially improves MDS risk stratification over the IPSS-R by incorporating somatic mutation data, restratifying ~46% of patients to different risk...
• PANTHER Blood Adv 2022
  Pevonedistat + azacitidine did not significantly improve EFS or OS versus azacitidine alone in higher-risk MDS or AML with low blast count. Post-hoc analyses...
• HCT in 50-75yo MDS JCO 2021
  In patients aged 50-75 with intermediate-2/high-risk MDS who are RIC-eligible and have a matched donor, RIC allo-HCT significantly improved 3-year OS and LFS versus...
• MEDALIST NEJM 2020
  Luspatercept significantly increased transfusion independence rates compared with placebo in ESA-refractory/ineligible LR-MDS with ring sideroblasts, establishing a...
• ONTIME (rigosertib: negative) Lancet Oncol 2016
  Rigosertib IV did not improve OS versus best supportive care in higher-risk MDS after HMA failure (mOS 6.1 vs 5.9 months, HR 0.87, P=.33). ONTIME is a key negative...
• DACO-016 JCO 2011
  Decitabine administered in 6-week cycles did not achieve a statistically significant OS improvement over BSC in older, chemotherapy-ineligible HR-MDS patients, though...
• MDS-004 Blood 2011
  Both lenalidomide doses produced significantly superior transfusion independence vs placebo in del5q LR-MDS. The 10 mg dose achieved higher cytogenetic response...
• AZA in High Risk MDS Clinical Trial Lancet Oncol 2009
  Azacitidine significantly prolonged median OS (24.5 vs 15.0 months, HR 0.58, P=.0001) and delayed AML transformation compared with conventional care regimens in...
• MDS-003 NEJM 2006
  Lenalidomide produced rapid, durable transfusion independence in two-thirds of transfusion-dependent del5q MDS patients, with concurrent cytogenetic and cytologic...

CML (15)

• Olverembatinib (global phase 1b) JAMA Oncol 2025
  Olverembatinib achieved ~61% CCyR and ~42% MMR in heavily pretreated CP-CML, including patients who had failed both ponatinib and asciminib. Activity was irrespective...
• ASC4FIRST NEJM 2024
  Asciminib significantly improved MMR at 48 weeks versus investigator's choice TKI in newly diagnosed CP-CML (67.7% vs 49.0%, P<.001) and versus imatinib specifically...
• ASCEMBL Blood 2021
  Asciminib significantly improved MMR at 24 weeks versus bosutinib in ≥3rd-line CP-CML (25.5% vs 13.2%, P=.029), with sustained MMR advantage at 96 and 156 weeks and...
• OPTIC Blood 2021
  OPTIC established that a 45 mg starting dose with reduction to 15 mg on achieving BCR-ABL ≤1% provides the best balance of efficacy (44.7% ≤1% rate at 12 months) and...
• EURO-SKI Lancet Oncol 2018
  EURO-SKI confirmed that approximately 50% of CML patients in sustained MR4 on any TKI can maintain treatment-free remission for ≥24 months after stopping, with all...
• BFORE trial JCO 2017
  First-line bosutinib produced higher and deeper molecular and cytogenetic responses at 12 months than imatinib, with a distinct gastrointestinal and hepatic toxicity...
• EPIC (terminated) Lancet Oncol 2016
  EPIC showed numerically superior early molecular responses for ponatinib vs imatinib in 1L CML but was terminated prematurely due to excess vascular events...
• PACE NEJM 2013
  Ponatinib achieved a 56% MCyR in heavily pretreated or T315I-mutant CP-CML - uniquely active against T315I (70% MCyR) - filling a critical unmet need as no other...
• Bosutinib post-2 prior TKIs (NCT00261846) Blood 2012
  Bosutinib achieved a 32% MCyR in CP-CML after failure of ≥2 prior TKIs, confirming activity in multiply pretreated patients without T315I mutation. Response rates are...
• Bosutinib post-imatinib (NCT00261846) Blood 2011
  Bosutinib achieved a 53% MCyR and 41% CCyR in imatinib-resistant or intolerant CP-CML with a 4-year PFS of 57%, supporting its approval as a 2nd-line CML option....
• DASISION trial NEJM 2010
  Dasatinib produced faster and deeper cytogenetic and molecular responses than imatinib, but at 5 years there was no difference in PFS or OS between the two first-line...
• ENESTend trial NEJM 2010
  Nilotinib significantly improved MMR, deep molecular response (MR4.5), and lowered progression to AP/BP CML versus imatinib, though 10-yr OS and PFS were similar...
• SPIRIT (French) NEJM 2010
  Imatinib + IFN-α2a achieved a statistically higher MR3 rate at 12 months versus imatinib alone (30.1% vs 14.5%) but with 61% grade ≥3 toxicity and 48% treatment...
• STIM Lancet Oncol 2010
  STIM demonstrated for the first time that approximately 40% of CML patients with ≥2 years of PCR-undetectable remission on imatinib can successfully stop therapy and...
• IRIS trial NEJM 2003
  Landmark trial that transformed CML management: imatinib was superior to IFN-alfa/cytarabine in cytogenetic response, progression-free survival, and tolerability...

HCL (5)

• ROAR (HCL cohort) Blood 2023
  Dabrafenib + trametinib achieved an 89% ORR and 56% CR in R/R BRAF V600E-mutated HCL, with a 2-year PFS of 78%, establishing the BRAF + MEK inhibitor doublet as an...
• Venetoclax + Obinutuzumab (HCL/HCLv) NEJM Evid 2023
  Venetoclax + obinutuzumab achieved a 68% CR rate and 97% ORR in R/R HCL/HCLv with 89% 2-year PFS - notably including HCL variant (BRAF WT), which does not respond to...
• Cladribine in HCL Blood Cancer J 2022
  A single 7-day course of cladribine achieved a 76% CR rate and 97% ORR in treatment-naive HCL, with 87% OS at 20 years, confirming cladribine as a highly effective...
• Vemurafenib + Rituximab (HCL) NEJM 2021
  Vemurafenib + rituximab achieved a 100% CR rate with 87% uMRD negativity in purine-analog R/R HCL, with 78% 3-year RFS - the deepest remission data reported in R/R...
• MOXIE Leukemia 2018
  Moxetumomab pasudotox achieved a 41% CR rate and 75% ORR in heavily pretreated R/R HCL with durable remissions (97% 2-yr DFS in uMRD-negative CRs), supporting FDA...