CurrentCentenePolicy CP.PHAR.366

Acalabrutinib (Calquence) (PDF)

Defines clinical medical necessity criteria, prior authorization expectations, approved indications (MCL, CLL/SLL) and selected NCCN-supported off-label B-cell lymphoma uses (WM/LPL, MZL), dosing limits, and approval durations for Centene lines of business.

Policy Summary

PayerCentene

PolicyAcalabrutinib (Calquence) (PDF)

Policy CodePolicy CP.PHAR.366

Change TypeAnnual review & RT4 updates

Effective DateMar 1, 2019

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

1Q 2026 annual review: added NCCN-supported uses including first-line therapy for CLL/SLL with Venclexta and single-agent therapy following Richter transformation; updated initial auth durations from 6 months to 12 months for Medicaid/HIM.

RT4: updated conditions to align first-line CLL/SLL use with FDA AMPLIFY trial PI addition.

Added exclusion that Calquence is not prescribed concurrently with Imbruvica or Brukinsa for WM/LPL and MZL; clarified MZL subtypes and relapsed/refractory requirement per NCCN.

Clarified generic redirection language to 'must use' and consolidated approval durations across lines of business.

3FDA-approved indications

3NCCN-supported off-label uses

400 mg/dayMax daily dose

Coverage Summary

Policy CP.PHAR.366 (CURRENT) — Acalabrutinib (Calquence) is covered with criteria for FDA‑approved indications (mantle cell lymphoma [MCL] and chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL]) and selected NCCN‑supported off‑label B‑cell lymphoma uses (Waldenström macroglobulinemia/lymphoplasmacytic lymphoma [WM/LPL] and marginal zone lymphoma [MZL] variants). Coverage requires meeting the listed medical necessity criteria and prior authorization expectations. The policy specifies a maximum daily dose of 400 mg/day (4 capsules or 4 tablets) and a standard approval duration of 12 months (with a ≤14‑cycle total duration when used in combination with venetoclax as first‑line CLL/SLL without del(17p)/TP53).

Initial Therapy Criteria

Initial Approval Criteria

Calquence is medically necessary when ALL of the following for the specified indication are met:

Continuation / Renewal Criteria

All indications in Section I: must meet all

ALL of the following

Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Calquence for a covered indication and has received this medication for at least 30 days30 days
Member is responding positively to therapy
For requests for combination use with Venclexta as first-line therapy for CLL/SLL in members without the del(17p)/TP53 mutation, the total duration of therapy will not exceed 14 cycles≤ 14 cycles
See Dosage and Administration for cycle definitions.
Member must use generic acalabrutinib, if available, unless contraindicated or clinically significant adverse effects are experienced
Prescriber must document contraindication or adverse effects to brand use.
If request is for a dose increase
- New dose does not exceed 400 mg (4 capsules or 4 tablets) per day400 mg/day
- New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Provider Actions / Prior Authorization

Prior Authorization

Submit documentation for medical necessity

Provider must submit office chart notes, laboratory results, or other clinical information supporting that the member has met all approval criteria for the requested use of Calquence.

Documentation Required

Prescriber specialty

Requests must be prescribed by or in consultation with an oncologist or hematologist for all covered indications.

Applicable Codes / Product Availability

Product availability (no billing codes provided)mixed

N/A	Tablet: 100 mg; Capsule: 100 mg (product availability only, no NDCs or billing codes provided)

Clinical Evidence & Rationale

Primary sources reviewed include the Calquence prescribing information (Feb 2026) and NCCN guidelines: CLL/SLL (Version 2.2026), B‑cell Lymphomas (Version 3.2025), and Waldenström's Macroglobulinemia/LPL (Version 1.2026).

Key evidence and background notes: the policy cites the Calquence PI (Feb 2026) and NCCN guidance; it documents that Calquence shows lack of activity in ibrutinib‑refractory disease with BTK C481S mutations and therefore is not recommended in Imbruvica‑refractory CLL/SLL or MCL with BTK C481S, while NCCN permits use in ibrutinib‑intolerant CLL/SLL. The policy changes note alignment with the FDA update adding AMPLIFY trial results to the Calquence PI and corresponding updates to first‑line CLL/SLL conditions.

Background & Definitions

Acalabrutinib (Calquence) is a Bruton tyrosine kinase (BTK) inhibitor and is FDA‑approved for MCL (first‑line in combination with bendamustine + rituximab for patients ineligible for autologous HSCT; and for patients with ≥1 prior therapy) and for CLL/SLL. NCCN recommendations have been incorporated into the policy to support selected off‑label B‑cell lymphoma uses (WM/LPL and MZL variants) and to guide regimen selection and sequencing.

The policy notes that due to lack of activity with BTK C481S mutations, Calquence should not be used for ibrutinib‑refractory CLL/SLL or MCL with this mutation; however, for CLL/SLL, Calquence may be used in cases of ibrutinib intolerance per NCCN. Dosage guidance in the policy follows the PI (typically 100 mg PO twice daily; maximum 400 mg/day), and recent updates aligned first‑line CLL/SLL criteria with the FDA's addition of AMPLIFY trial data to the Calquence PI.

Term	Definition
BTK C481S mutation	A mutation in Bruton's tyrosine kinase associated with resistance to ibrutinib (Imbruvica); Calquence not recommended for Imbruvica-refractory disease with this mutation.
NCCN	National Comprehensive Cancer Network
HSCT	Hematopoietic stem cell transplantation

Revision History

2026-03-06revisedLatest

RT4: updated conditions for first-line CLL/SLL use to align with FDA approval adding AMPLIFY trial results to the Calquence prescribing information.

2026-02-26added

P&T Approval Date = 02.26.26: 1Q 2026 annual review added NCCN-supported uses including first-line therapy for CLL/SLL with Venclexta and single-agent therapy following Richter transformation; updated initial authorization durations from 6 months to 12 months for Medicaid/HIM; references reviewed and updated.

2022-2025 (cumulative)revised