What is the efficacy of Calcquence (acalabrutinib) in adult patients with small lymphocytic lymphoma (SLL)?

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Last updated: February 12, 2026 • View editorial policy

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Efficacy of Calquence (Acalabrutinib) in Small Lymphocytic Lymphoma

Acalabrutinib demonstrates excellent efficacy in SLL with an overall response rate of 76-97% and is now a Category 1 preferred regimen for relapsed/refractory disease, with particularly strong evidence supporting its use either as monotherapy or in combination with obinutuzumab. 1

Treatment-Naive SLL: First-Line Therapy

Acalabrutinib + Obinutuzumab (Category 2A)

  • Overall response rate of 94% (13% complete response rate) in the ELEVATE-TN trial 1
  • 2-year progression-free survival (PFS) rate of 93% compared to 47% with chlorambucil + obinutuzumab 1
  • 5-year follow-up data shows sustained benefit with superior PFS (HR 0.11,95% CI 0.07-0.67, P<0.0001) and overall survival (HR 0.55,95% CI 0.30-0.99) versus chlorambucil + obinutuzumab 1
  • PFS benefit maintained across all subgroups including IGHV unmutated and mutated disease 1

Acalabrutinib Monotherapy

  • Overall response rate of 85% (entirely partial responses) in ELEVATE-TN 1
  • 2-year PFS rate of 87% 1
  • In a treatment-naive cohort (ACE-CL-001 trial), 97% overall response rate with 48-month duration of response rate of 97% 2
  • Median duration of response not reached after 53 months median follow-up 2

The study was not powered to compare acalabrutinib monotherapy versus acalabrutinib + obinutuzumab directly, so the incremental benefit of adding obinutuzumab remains unclear, though combination therapy shows consistent observational benefit. 1

Relapsed/Refractory SLL: Category 1 Preferred Regimen

Efficacy in Previously Treated Disease

  • Overall response rate of 81% in the ASCEND trial comparing acalabrutinib to idelalisib-rituximab or bendamustine-rituximab 1
  • 1-year PFS rate of 88% versus 68-69% for chemotherapy-based regimens 1
  • Median PFS not reached at 16-month follow-up (P<0.0001 versus comparators) 1
  • Upgraded from Category 2A to Category 1 (preferred regimen) based on ASCEND trial results 1

Special Populations

High-Risk Disease (del(17p)/TP53 mutation):

  • Overall response rate of 85% in patients with del(17p) 1
  • 18-month PFS not reached in this high-risk subgroup 1
  • Del(17p) present in 9-10% and TP53 mutations in 11-12% of ELEVATE-TN patients, with maintained PFS benefit 1

Ibrutinib-Intolerant Patients:

  • 76% overall response rate (including PR with lymphocytosis) in 33 patients who discontinued ibrutinib due to intolerance 1
  • Estimated 2-year PFS rate of 75% after median 19-month follow-up 1
  • Successfully treated without recurrence of ibrutinib-related symptoms 1

Critical caveat: Acalabrutinib is NOT effective for ibrutinib-refractory CLL/SLL with BTK C481S mutations 1

Comparative Efficacy Context

Acalabrutinib demonstrates comparable or superior efficacy to other BTK inhibitors while offering a more favorable cardiovascular safety profile:

  • Lower rates of atrial fibrillation (4-7% overall, 1% grade ≥3) compared to ibrutinib 3, 4
  • Lower rates of hypertension (3-7% overall, 2-3% grade ≥3) 3, 4
  • Preferred over ibrutinib in patients with cardiovascular comorbidities 1

Duration of Treatment and Long-Term Outcomes

  • Acalabrutinib is administered continuously until disease progression 1
  • In treatment-naive patients, 85 of 99 patients (86%) remained on treatment after 53 months median follow-up 2
  • Only 6% discontinued due to adverse events in long-term follow-up 2
  • 48-month duration of response rate of 97% demonstrates sustained disease control 2

Clinical Algorithm for SLL Treatment Selection

For treatment-naive SLL:

  1. Consider acalabrutinib + obinutuzumab for maximum response rates (94% ORR, 13% CR) 1
  2. Consider acalabrutinib monotherapy if obinutuzumab contraindicated or to minimize neutropenia risk (30% grade ≥3 with combination vs 10% with monotherapy) 1
  3. Both options are appropriate regardless of age, comorbidities, or IGHV status 1

For relapsed/refractory SLL:

  1. Acalabrutinib is Category 1 preferred regardless of age and comorbidities 1
  2. Effective after prior chemoimmunotherapy with 81% ORR 1
  3. Viable option for ibrutinib-intolerant patients (76% ORR) 1
  4. Do NOT use if patient has documented BTK C481S mutation from prior ibrutinib resistance 1

For high-risk SLL (del(17p)/TP53 mutation):

  • Acalabrutinib efficacy (85% ORR) exceeds other regimens and should be considered best choice 1
  • Maintained PFS benefit across all cytogenetic subgroups 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Acalabrutinib Side Effects and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

4
Guideline

Acalabrutinib Side Effects and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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