Acalabrutinib (Calquence) coverage
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Medical necessity and prior authorization criteria for acalabrutinib (Calquence) for adult patients with mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and selected off-label B-cell malignancies; applies to providers and members covered under the payer's Commercial, HIM and Medicaid lines of business.
Added NCCN-supported use: first-line therapy for CLL/SLL in combination with venetoclax (Venclexta).
Updated initial authorization durations from 6 months to 12 months for Medicaid/HIM.
Updated conditions for first-line use in CLL/SLL to align with recent FDA approval adding AMPLIFY trial results to the Calquence PI.
Added tablet formulation dosing/regimen language and tablet product availability.
Coverage Criteria
Initial Therapy: Mantle Cell Lymphoma
Covered when ALL of the following are met
Prescribed regimen must be FDA-approved or recommended by NCCN.
Initial Therapy: CLL/SLL
Covered when ALL of the following are met
Prescribed regimen must be FDA-approved or recommended by NCCN; when combined with venetoclax/obinutuzumab follow specific cycle sequencing and durations per dosing guidance.
Initial Therapy: Waldenstrom Macroglobulinemia / LPL (off‑label)
Covered when ALL of the following are met
Prior authorization may be required; prescribed regimen must be FDA-approved or recommended by NCCN when applicable.
Initial Therapy: Marginal Zone Lymphoma (off‑label)
Covered when ALL of the following are met
Prior authorization may be required; prescribed regimen must be FDA-approved or recommended by NCCN when applicable.
Continuation Therapy
Covered when ALL of the following are met
Prescribed regimen must be FDA-approved or recommended by NCCN.
Coverage criteria (high-level)
Covered when aligned with FDA approval and NCCN-supported indications and when dosing/regimen matches prescribing information:
See disease-specific dosing and sequencing guidance in the dosing section.
Refer to dosing table for exact cycle timing.
Authorization durations updated and maintenance use for MCL removed per recent updates.
See disease-specific sections for per-disease restrictions.
Requests for non‑FDA approved indications that are not specifically addressed in this policy will be excluded unless the prescriber provides sufficient documentation of efficacy and safety in accordance with the payer's off‑label use policies (for example, CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, or CP.PMN.53 for Medicaid).
The policy includes an explicit exclusion for Imbruvica‑refractory mantle cell lymphoma (MCL) with a BTK C481S mutation; use in that setting may be denied. In addition, the policy states that Calquence should not be prescribed concurrently with other BTK inhibitors (for example, Imbruvica or Brukinsa) in certain B‑cell indications such as Waldenström macroglobulinemia, LPL, and marginal zone lymphoma.
Per the policy and supporting NCCN guidance, acalabrutinib (Calquence) lacks activity in ibrutinib‑refractory disease when a BTK C481S mutation is present; therefore use in ibrutinib‑refractory CLL/SLL or MCL with BTK C481S mutations is considered not appropriate.
The policy clarifies that, in line with NCCN guidance, Calquence is not appropriate for Imbruvica‑refractory CLL/SLL if a BTK C481S mutation is present. This position was incorporated into the policy during routine updates to align with guideline recommendations.
Coding
| N/A | No explicit CPT/HCPCS/ICD-10/NDC codes listed in this part of the document |
| N/A | Document cites guideline and prescribing information updates but does not list specific CPT/HCPCS/NDC codes in this excerpt. |
Provider Actions & Requirements
Prior Authorization Required
Prior authorization is required for Calquence (acalabrutinib) requests. Providers must submit documentation (office notes, labs, pathology, prior therapy details, mutation testing) that supports the member meets all applicable approval criteria, including diagnosis, prescriber specialty, age, prior therapies or specified combination regimens, and absence of excluded BTK C481S mutation where applicable. Requests for off‑label regimens must include supporting evidence (peer‑reviewed literature or guideline citations).
- Affected indications: MCL, CLL/SLL, WM/LPL, MZL and other policy‑listed diagnoses
- Authorization durations: initial approvals updated per policy (see policy header/criteria) — initial authorizations for Medicaid/HIM updated from 6 to 12 months where applicable
- Off‑label use: prescriber must submit supporting evidence (guideline or literature)
Dosing & Formulation Documentation
Prescribers must document dosing regimen and product formulation on the PA submission. For MCL and CLL/SLL the usual dosing is 100 mg PO twice daily (maximum 400 mg/day). For combination regimens (e.g., with obinutuzumab or venetoclax) specify cycle timing and sequence per product labeling/NCCN (for example: start acalabrutinib 100 mg PO BID at Cycle 1 and start obinutuzumab at Cycle 2 when indicated; when used with venetoclax in frontline CLL/SLL, acalabrutinib is started at Cycle 1 and venetoclax at Cycle 3 per regimen guidance). Indicate whether tablet or capsule (100 mg) formulation will be used and note if generic acalabrutinib will be used unless contraindicated.
- Standard dosing: 100 mg PO BID (tablet or capsule, 100 mg)
- Maximum dose: 400 mg/day
- Combination regimen documentation: specify cycle length, timing (which cycle each agent is initiated), and sequence
Step Therapy / Prior BTK Inhibitor Requirements
Step‑therapy and prior BTK inhibitor requirements: where prior‑therapy criteria apply, providers must document prior lines of therapy per the policy (see Appendix B for therapeutic alternatives). The policy excludes use for Imbruvica‑refractory disease with documented BTK C481S mutation for MCL and clarifies Calquence is not to be used in Imbruvica‑refractory CLL/SLL with BTK C481S mutations. The policy no longer universally requires prior trial of a BTK inhibitor before Calquence for all indications; check indication‑specific initial criteria (some indications may require ≥1 prior therapy or specific combination settings).
- Therapeutic alternatives may be required — see Appendix B
- Exclusion: Imbruvica‑refractory MCL or CLL/SLL with BTK C481S mutation — document mutation testing if claiming non‑refractory status
- Prior BTK inhibitor: prior use of Imbruvica is not universally required; follow indication‑specific criteria
Background
Acalabrutinib (Calquence) is a Bruton tyrosine kinase (BTK) inhibitor indicated for adult patients with mantle cell lymphoma (MCL) and for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) per the product labeling and updated approvals. The policy notes that Calquence can be used in approved and certain NCCN‑supported regimens (including updated first‑line combinations in CLL/SLL), but it also documents limited activity in ibrutinib‑refractory disease with BTK C481S mutations and therefore excludes use in that molecular context.
Definitions
Line of Therapy
first-line | second-line | subsequent
first-line
AMPLIFY trial results added to the Calquence PI; policy aligned to allow these regimens.
second-line
Refer to disease-specific initial therapy sections for exact prior-therapy requirements and exclusions.
Biomarker & Mutation Requirements
Covered Regimens and Dosing
| Regimen | Indication | Coverage status |
|---|---|---|
| Acalabrutinib 100 mg PO BID; monotherapy or in combination per FDA labeling | ||
| Mantle cell lymphoma (MCL): as monotherapy for patients who have received ≥1 prior therapy, or in combination with bendamustine + rituximab for previously untreated patients who are ineligible for autologous HSCT | ||
| Dose not to exceed 400 mg/day (4 capsules or 4 tablets) unless supported by guidelines or literature |
| Regimen | Patient selection / biomarker requirement | Duration / Coverage status |
|---|---|---|
| Acalabrutinib 100 mg PO BID in combination with venetoclax (with or without obinutuzumab) | ||
| Previously untreated CLL/SLL without del(17p)/TP53 mutation | ||
| Total duration when used with venetoclax in first-line (patients without del(17p)/TP53): not to exceed 14 cycles (Calquence up to 14 cycles; venetoclax total 12 cycles). Coverage: covered with criteria |
| Regimen | Restrictions | Coverage status |
|---|---|---|
| Acalabrutinib 100 mg PO BID as single agent | ||
| May be used off-label for Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) as second-line or subsequent therapy; must NOT be prescribed concurrently with ibrutinib (Imbruvica) or zanubrutinib (Brukinsa); prior authorization may be required | ||
| Off-label use covered when criteria met; coverage with criteria (restricted) |
| Regimen | Cycle timing | Coverage status |
|---|---|---|
| Calquence (acalabrutinib) 100 mg PO BID combined with obinutuzumab (Gazyva) | ||
| Start Calquence at Cycle 1 (28-day cycles); start Gazyva at Cycle 2 for a total of 6 cycles; administer Calquence prior to Gazyva when given the same day | ||
| Covered for previously untreated CLL/SLL per regimen and criteria |
| Regimen | Cycle timing / duration | Coverage status |
|---|---|---|
| Calquence (acalabrutinib) 100 mg PO BID in combination with venetoclax | ||
| Start Calquence at Cycle 1 (28-day cycles) for up to 14 cycles; start venetoclax at Cycle 3 for a total of 12 cycles | ||
| Covered for previously untreated CLL/SLL without del(17p)/TP53 when criteria met; total duration not to exceed 14 cycles for Calquence |
| Parameter | Value | Notes / Policy alignment |
|---|---|---|
| Typical dosing regimen | ||
| 100 mg PO BID | ||
| MCL and CLL/SLL standard dosing per prescribing information and policy (see dosing section). |
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