Evidence-Based Learning

Journal Club &
Critical Appraisal

Structured summaries and critical appraisal of landmark haematology trials and high-impact publications — designed for trainees and practising clinicians.

3
Papers reviewed
4
BSH divisions covered
RCT
Level 1 evidence focus
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Showing 6 entries

Malignant Haematology NEJM 2022

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

Tilly H et al. N Engl J Med 2022;386:351–363 — POLARIX Trial (Phase III RCT)

Key Findings

  • 2-year progression-free survival: 76.7% with Pola-R-CHP vs 70.2% with R-CHOP (statistically significant)
  • No significant overall survival difference at primary analysis — longer follow-up awaited
  • Peripheral neuropathy rates were comparable between arms (52.9% vs 53.9% any grade), with fewer dose reductions required in the polatuzumab arm (4.4% vs 8.0%)
Clinical Takeaway

Pola-R-CHP is now an established front-line option for intermediate- and high-risk DLBCL, replacing vincristine with a targeted antibody-drug conjugate. The absence of an OS benefit at primary analysis means R-CHOP remains reasonable, particularly in lower-risk or elderly patients.

Critical Appraisal Note

Double-blind RCT with robust design. Key limitation: the OS benefit was not demonstrated at primary analysis. Patient selection (IPI ≥2) limits generalisability to low-risk disease. Five-year follow-up data presented at ASH 2024 showed sustained PFS advantage.

1A Level 1 Evidence — Phase III RCT
Haemostasis & Thrombosis NEJM 2020

Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer

Agnelli G et al. N Engl J Med 2020;382:1599–1607 — CARAVAGGIO Trial (Phase III RCT)

Key Findings

  • Recurrent VTE: 5.6% with apixaban vs 7.9% with dalteparin (HR 0.63; 95% CI 0.37–1.07; P<0.001 for non-inferiority)
  • Major bleeding: 3.8% vs 4.0% — no significant increase with apixaban (HR 0.82; 95% CI 0.40–1.69; P=0.60)
  • Oral administration of apixaban was non-inferior to subcutaneous dalteparin across all cancer subtypes analysed
Clinical Takeaway

Apixaban is non-inferior to dalteparin for cancer-associated VTE without a significantly increased bleeding risk, making it a practical oral alternative to low-molecular-weight heparin in eligible patients. Caution remains warranted in GI and genitourinary malignancies due to historically higher mucosal bleeding rates with DOACs in these tumour types.

Critical Appraisal Note

Well-designed investigator-initiated RCT. Non-inferiority design: the CI upper bound (1.07) does not exclude a small increase in recurrent VTE. Patients with GI and GU cancers at higher bleeding risk were not excluded — clinicians should apply individual risk stratification in these groups.

1A Level 1 Evidence — Phase III RCT
Malignant Haematology NEJM 2018

Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukaemia

Seymour JF et al. N Engl J Med 2018;378:1107–1120 — MURANO Trial (Phase III RCT)

Key Findings

  • At median 36-month follow-up: PFS markedly superior with VenR vs bendamustine-rituximab (HR 0.16; 95% CI 0.12–0.23)
  • Overall survival also superior (HR 0.50; 95% CI 0.30–0.85) — a rare demonstration of OS benefit in r/r CLL
  • Undetectable MRD at end of combination therapy: 62% with VenR vs 13% with BR — establishing fixed-duration treatment as a feasible strategy
Clinical Takeaway

MURANO established fixed-duration venetoclax-rituximab as a preferred option for relapsed/refractory CLL, particularly for patients unsuitable for indefinite BTK inhibitor therapy. The high rate of undetectable MRD supports a time-limited treatment strategy with potential for treatment-free remission.

Critical Appraisal Note

Phase III RCT with meaningful OS benefit — a high bar in the CLL field. Comparator arm (BR) may be considered suboptimal by current standards. Tumour lysis syndrome risk requires a structured ramp-up protocol, limiting use to centres with appropriate monitoring infrastructure.

1A Level 1 Evidence — Phase III RCT
General Haematology Coming Soon

Iron Deficiency — Intravenous vs Oral Iron in Anaemia Management

Critical appraisal of RCT evidence comparing IV and oral iron formulations in iron deficiency anaemia — covering efficacy, adverse effects, and practical prescribing guidance.

Transfusion Medicine Coming Soon

Restrictive vs Liberal Red Cell Transfusion Thresholds — Evidence Review

Summary and appraisal of landmark trials including TRICC and TRISS examining haemoglobin transfusion triggers across critical care, cardiac, and haematology patient populations.

Haemostasis & Thrombosis Coming Soon

Extended Anticoagulation in Unprovoked VTE — Balancing Recurrence vs Bleeding Risk

Appraisal of evidence for extended anticoagulation beyond 3–6 months in unprovoked VTE, including AMPLIFY-EXT and EINSTEIN CHOICE, with guidance on risk stratification tools.