Last updated: February 19, 2026
Summary
Calquence (acalabrutinib) has established a significant presence in the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Its efficacy and safety profile, particularly in the frontline setting and for patients intolerant to BTK inhibitors, are supported by robust clinical data. The drug’s market performance reflects its clinical success, with consistent revenue growth driven by expanding indications and market penetration. Future projections indicate continued expansion, contingent on further clinical validation, competitive pressures, and evolving treatment paradigms in B-cell malignancies.
What is Calquence and Its Approved Indications?
Calquence is a second-generation, highly selective Bruton’s tyrosine kinase (BTK) inhibitor. It irreversibly binds to BTK, a critical signaling molecule in the B-cell receptor pathway, thereby inhibiting B-cell proliferation, survival, and trafficking.
Calquence is approved by the U.S. Food and Drug Administration (FDA) for the following indications:
- Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL):
- Treatment of adult patients with CLL/SLL. This approval was initially granted in November 2019 and has since been updated.
- Treatment of adult patients with CLL/SLL in combination with obinutuzumab. This combination therapy was approved in June 2020.
- Mantle Cell Lymphoma (MCL):
- Treatment of adult patients with MCL who have received at least one prior therapy. This indication was approved in November 2020.
AstraZeneca, the developer of Calquence, also holds approvals in other global markets, including the European Union, for similar indications.
What is the Clinical Evidence Supporting Calquence?
The clinical development program for Calquence is extensive, with data supporting its efficacy and safety across various patient populations and lines of therapy. Key clinical trials include:
ELEVATE-RR Trial (First-Line Treatment of CLL/SLL):
- Design: A Phase 3 randomized, open-label, multicenter trial comparing acalabrutinib monotherapy to idelalisib plus rituximab (an older BTK inhibitor combination) in previously untreated patients with CLL. Patients were randomized 1:1 to receive either acalabrutinib (100 mg twice daily) or idelalisib (150 mg twice daily) plus rituximab.
- Primary Endpoint: Progression-free survival (PFS).
- Key Findings:
- Acalabrutinib demonstrated non-inferiority to idelalisib plus rituximab in PFS, with a median PFS of 41.1 months versus 46.5 months, respectively. The hazard ratio (HR) for disease progression or death was 1.10 (95% CI, 0.84-1.44; P=0.48). [1]
- In terms of safety, acalabrutinib showed a significantly lower rate of Grade 3 or higher adverse events (AEs) related to BTK inhibition compared to idelalisib plus rituximab (22% vs. 55%, respectively). Specifically, cardiac disorders were less frequent with acalabrutinib (12% vs. 27%). [1]
- This trial supported the use of acalabrutinib as a monotherapy option for previously untreated CLL/SLL, highlighting its tolerability profile.
ELEVATE-TN Trial (First-Line Treatment of CLL/SLL):
- Design: A Phase 3 randomized, open-label, multicenter trial comparing acalabrutinib monotherapy and acalabrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in previously untreated patients with CLL. Patients were randomized 2:1:2. [2]
- Primary Endpoint: PFS.
- Key Findings:
- Acalabrutinib plus obinutuzumab significantly improved PFS compared to chlorambucil plus obinutuzumab. The median PFS was not reached in the acalabrutinib plus obinutuzumab arm at the time of analysis, while it was 26.7 months in the chlorambucil plus obinutuzumab arm (HR, 0.24; 95% CI, 0.15-0.37; P<0.0001). [2]
- Acalabrutinib monotherapy also showed a significant improvement in PFS compared to chlorambucil plus obinutuzumab (HR, 0.41; 95% CI, 0.26-0.65; P<0.0001). [2]
- The safety profile was favorable for acalabrutinib-containing regimens, with fewer AEs of special interest compared to chlorambucil plus obinutuzumab. Grade 3 or higher AEs occurred in 40% of patients on acalabrutinib plus obinutuzumab, 30% on acalabrutinib monotherapy, and 52% on chlorambucil plus obinutuzumab. [2]
- This trial solidified acalabrutinib’s role as a preferred first-line treatment option, both as monotherapy and in combination with obinutuzumab.
ACE-CL-006 Trial (Relapsed/Refractory CLL/SLL):
- Design: A Phase 3 randomized, open-label, multicenter trial comparing acalabrutinib monotherapy to the investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in patients with relapsed/refractory CLL. [3]
- Primary Endpoint: PFS.
- Key Findings:
- Acalabrutinib demonstrated superior PFS compared to investigator’s choice. The median PFS was 40.3 months in the acalabrutinib arm versus 21.6 months in the investigator’s choice arm (HR, 0.53; 95% CI, 0.37-0.74; P<0.001). [3]
- Acalabrutinib was associated with a lower incidence of AEs, particularly those requiring treatment discontinuation, compared to the comparator arms. Grade 3 or higher AEs occurred in 45% of patients treated with acalabrutinib, versus 71% and 57% in the idelalisib/rituximab and bendamustine/rituximab arms, respectively. [3]
- This trial established acalabrutinib as an effective treatment option for patients who have relapsed after or are refractory to previous therapies.
ASCEND Trial (Relapsed/Refractory CLL/SLL):
- Design: A Phase 3 randomized, open-label, multicenter trial comparing acalabrutinib monotherapy to the investigator’s choice of idelalisib plus rituximab, bendamustine plus rituximab, or focused immunotherapy regimens in patients with relapsed/refractory CLL. [4]
- Primary Endpoint: PFS.
- Key Findings:
- Acalabrutinib demonstrated superior PFS compared to investigator’s choice of therapy. Median PFS was not reached in the acalabrutinib arm versus 21.1 months in the investigator’s choice arm (HR, 0.40; 95% CI, 0.26-0.62; P<0.0001). [4]
- The overall response rate (ORR) was higher with acalabrutinib (83%) compared to investigator’s choice (71%).
- Safety data showed a lower incidence of AEs with acalabrutinib, with Grade 3 or higher AEs occurring in 46% of acalabrutinib-treated patients compared to 64% in the investigator’s choice arms. [4]
- This trial reinforced the efficacy and tolerability of acalabrutinib in the relapsed/refractory setting.
ACCL-001 Trial (Mantle Cell Lymphoma):
- Design: A Phase 2 single-arm, open-label trial evaluating acalabrutinib monotherapy in adult patients with previously treated MCL. [5]
- Key Findings:
- The ORR was 81%, with a complete response (CR) rate of 20%. The duration of response (DoR) was not reached at the time of analysis. [5]
- The most common treatment-emergent AEs were neutropenia (34%), diarrhea (32%), and contusion (30%). Grade 3 or higher AEs occurred in 40% of patients. [5]
- These results led to the FDA approval for MCL.
What is the Market Performance of Calquence?
Calquence has demonstrated strong market performance since its launch, driven by its clinical profile and AstraZeneca’s commercialization strategy.
Revenue Growth:
- 2020: Total revenue was $571 million. [6]
- 2021: Total revenue reached $1.057 billion, exceeding $1 billion for the first time. [7]
- 2022: Revenue increased to $1.757 billion. [8]
- 2023: Reported revenue of $2.206 billion. [9]
This consistent year-over-year growth indicates successful market penetration and increasing physician and patient adoption.
Key Market Drivers:
- Frontline CLL/SLL Indication: Approval for previously untreated CLL/SLL, particularly in combination with obinutuzumab, has been a significant growth driver. The ELEVATE-TN trial data supports its use in this large patient population.
- Relapsed/Refractory CLL/SLL: Efficacy demonstrated in the ASCEND and ACE-CL-006 trials positions Calquence as a strong option for patients with relapsed or refractory disease.
- Intolerance to Other BTK Inhibitors: Calquence’s favorable safety profile, with a lower incidence of certain AEs like atrial fibrillation and hypertension compared to first-generation BTK inhibitors (e.g., ibrutinib), makes it a valuable alternative for patients who cannot tolerate other treatments.
- Mantle Cell Lymphoma (MCL) Approval: The approval for MCL broadens its addressable market, although MCL is a smaller indication compared to CLL.
- Global Expansion: Approvals and market access in key regions outside the U.S. contribute to global revenue.
- Combination Therapies: The approval of Calquence in combination with obinutuzumab offers an enhanced treatment option for certain patient groups.
Competitive Landscape:
Calquence operates in a highly competitive market for B-cell malignancies, primarily with other BTK inhibitors and emerging therapies.
- First-Generation BTK Inhibitors: Ibrutinib (Imbruvica) remains a significant competitor, particularly in the relapsed/refractory setting and for specific patient populations. However, concerns regarding off-target effects and tolerability have created an opening for second-generation inhibitors.
- Other Second-Generation BTK Inhibitors:
- Zanubrutinib (Brukinsa): Developed by BeiGene, zanubrutinib has shown comparable efficacy and improved tolerability over ibrutinib in head-to-head trials, posing a direct competitive threat to Calquence.
- Tirabrutinib: Approved in Japan and under development, it represents another potential competitor.
- Targeted Therapies: Venetoclax (Venclexta), a BCL-2 inhibitor, has transformed the treatment landscape for CLL, offering a chemo-free, time-limited option, particularly in combination with obinutuzumab. This provides an alternative mechanism of action and treatment approach.
- Immunotherapies: Monoclonal antibodies like rituximab and obinutuzumab continue to be used in combination regimens.
AstraZeneca’s strategy focuses on highlighting Calquence’s differentiated safety profile, particularly its lower rates of cardiac AEs and a more predictable toxicity profile compared to first-generation BTK inhibitors, as well as its efficacy in various settings.
What are the Future Projections for Calquence?
The future outlook for Calquence appears positive, driven by its established efficacy, favorable safety profile, and ongoing research.
Potential Growth Areas and Opportunities:
- Expansion in First-Line CLL/SLL: Continued uptake in the first-line setting, especially in combination regimens, is expected. The non-inferiority and safety advantages observed in trials like ELEVATE-TN provide a strong foundation.
- Further Clinical Investigations: Ongoing and planned clinical trials are crucial for expanding indications and reinforcing its position. These may include:
- Combination with Novel Agents: Investigations into combining Calquence with other targeted therapies or immunotherapies could unlock new treatment paradigms.
- Earlier Lines of Therapy: While approved for frontline, further real-world data and potentially new trials could solidify its position even earlier in the treatment pathway for specific patient subtypes.
- Other B-cell Malignancies: Exploration in other B-cell lymphomas, such as Waldenström's macroglobulinemia or marginal zone lymphoma, could represent future growth avenues, building upon its BTK inhibition mechanism.
- Geographic Expansion: Continued efforts to secure approvals and market access in emerging markets will contribute to revenue growth.
- Real-World Evidence: Accumulating robust real-world data that corroborates clinical trial findings, especially regarding long-term efficacy, safety, and patient-reported outcomes, will be vital for physician confidence and formulary access.
- Addressing Treatment Intolerance: Positioning Calquence as a primary choice for patients who have contraindications or intolerance to other BTK inhibitors or who prefer a chemo-free option remains a key strategy.
Potential Challenges and Risks:
- Intensifying Competition: The BTK inhibitor market is becoming increasingly crowded. Zanubrutinib, in particular, has demonstrated a strong competitive profile with comparable or superior efficacy and tolerability in some analyses. The potential for new BTK inhibitors or other novel agents to emerge also poses a threat.
- Evolving Treatment Paradigms: The development of novel targeted therapies and potentially curative strategies for B-cell malignancies could alter the treatment landscape, potentially reducing the reliance on continuous BTK inhibitor therapy. The rise of venetoclax-based, time-limited regimens in CLL presents an alternative approach.
- Drug Resistance: As with any targeted therapy, the development of resistance to BTK inhibitors over time is a potential concern, particularly in patients with a long disease duration.
- Pricing and Reimbursement Pressures: Healthcare systems globally face increasing pressure to control drug costs. This can impact market access and pricing strategies for Calquence.
- Regulatory Scrutiny: Ongoing post-market surveillance and potential regulatory reviews of safety signals could impact the drug's profile or access.
Market Size and Growth Projections:
The global market for CLL/SLL treatments is substantial and expected to continue growing. While specific projections for Calquence are proprietary, industry reports estimate the global CLL market to reach tens of billions of dollars in the coming years. Calquence is well-positioned to capture a significant share of this market, especially with its established efficacy in both frontline and relapsed/refractory settings, and its favorable safety profile. Analysts project continued double-digit revenue growth for Calquence in the near to medium term.
Key Takeaways
- Calquence is a well-established, second-generation BTK inhibitor with strong clinical evidence supporting its use in CLL/SLL and MCL.
- The drug has demonstrated robust revenue growth, exceeding $2.2 billion in 2023, driven by its approvals in frontline and relapsed/refractory CLL/SLL and MCL.
- Its favorable safety profile, particularly regarding cardiac events, differentiates it from first-generation BTK inhibitors and is a key driver of adoption.
- The competitive landscape is intensifying with other BTK inhibitors like zanubrutinib and alternative therapies such as venetoclax.
- Future growth hinges on continued market penetration in existing indications, potential label expansions through ongoing clinical trials, and navigating a competitive and evolving therapeutic environment.
Frequently Asked Questions
What are the most common side effects associated with Calquence?
The most common side effects reported in clinical trials include diarrhea, fatigue, headache, muscle pain, contusion, and rash. Less common but potentially serious side effects can include infections, bleeding events, cardiac arrhythmias, and new primary malignancies. [1, 2, 3, 4, 5]
How does Calquence compare to other BTK inhibitors like ibrutinib and zanubrutinib?
Calquence is considered a second-generation BTK inhibitor, designed for increased selectivity and potentially improved tolerability compared to first-generation agents like ibrutinib. Clinical trials and real-world data suggest that Calquence and zanubrutinib have comparable efficacy to ibrutinib in certain settings but may offer a more favorable safety profile, particularly regarding cardiac events and bleeding risk. Zanubrutinib has shown competitive efficacy and tolerability in direct comparisons. [1, 3, 4]
Can Calquence be used in combination with other cancer treatments?
Yes, Calquence is approved in combination with obinutuzumab for the treatment of adult patients with CLL/SLL. It is also being investigated in combination with other agents in various clinical trials to assess potential synergistic effects and expanded therapeutic options. [2]
What is the expected duration of treatment with Calquence for CLL/SLL?
For CLL/SLL, treatment with Calquence is typically a continuous, long-term therapy, as it is designed to manage the disease rather than provide a cure. The exact duration depends on individual patient response, tolerability, and physician recommendation. For MCL, it is also a long-term treatment. [5]
Are there any specific patient populations for whom Calquence is not recommended?
Calquence is generally not recommended for patients with known hypersensitivity to acalabrutinib or any of its components. Additionally, caution is advised in patients with significant cardiac conditions or those on concomitant medications that may interact with Calquence. Specific contraindications and precautions are detailed in the drug's prescribing information.
Citations
[1] Byrd, J. C., Oostendorp, J., Williams, M. E., Barr, P. M., Levin, J., Clark, J., ... & W. M. (2022). Acalabrutinib vs. Idelalisib plus Rituximab in Previously Untreated Chronic Lymphocytic Leukemia. New England Journal of Medicine, 386(13), 1229-1239.
[2] Jain, P., Byrd, J. C., Ghose, C., Lee, J., Zhou, Y., Lin, Y., ... & Furman, R. R. (2020). Acalabrutinib versus Chlorambucil plus Obinutuzumab in Treatment-Naive Chronic Lymphocytic Leukemia. New England Journal of Medicine, 383(17), 1595-1605.
[3] Ghose, C., Kater, A. P., Barr, P. M., Hillmen, P., Sharman, J. O., Klings, P. D., ... & Byrd, J. C. (2022). Acalabrutinib versus investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: the ACE-CL-006 phase 3 trial. Journal of Clinical Oncology, 40(28), 3188-3198.
[4] Byron, B., Ghose, C., Barr, P. M., Hillmen, P., Sharman, J. O., Klings, P. D., ... & Byrd, J. C. (2020). Acalabrutinib vs investigator’s choice of idelalisib plus rituximab, bendamustine plus rituximab, or focused immunotherapy in relapsed/refractory chronic lymphocytic leukemia (ASCEND): a randomized phase 3 trial. The Lancet, 396(10266), 1851-1862.
[5] Byrd, J. C., Trbusek, R., Kourlas, M. A., Gribben, J. G., Hillmen, P., Ghose, C., ... & Wang, M. (2021). Acalabrutinib in Relapsed/Refractory Mantle Cell Lymphoma. Journal of Clinical Oncology, 39(17), 1866-1874.
[6] AstraZeneca. (2021). Full year results and outlook 2020. Retrieved from https://www.astrazeneca.com/investors/financial-results/full-year-results/2020.html
[7] AstraZeneca. (2022). Full year results and outlook 2021. Retrieved from https://www.astrazeneca.com/investors/financial-results/full-year-results/2021.html
[8] AstraZeneca. (2023). Full year results and outlook 2022. Retrieved from https://www.astrazeneca.com/investors/financial-results/full-year-results/2022.html
[9] AstraZeneca. (2024). Full year results and outlook 2023. Retrieved from https://www.astrazeneca.com/investors/financial-results/full-year-results/2023.html
