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CurrentAetnaPolicy 0497

Hematopoietic Cell Transplantation for Multiple Myeloma

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Defines Aetna's medical necessity, selection criteria, coding, and exclusions for autologous, allogeneic, tandem, and reduced-intensity hematopoietic cell transplantation in members with multiple myeloma, amyloidosis, or POEMS syndrome.

Policy Summary

PayerAetna

PolicyHematopoietic Cell Transplantation for Multiple Myeloma

Policy CodePolicy 0497

Change TypeNo material change

Effective Date02/01/2002

Last ReviewAug 5, 2026

Next Review Date05/27/2027

Key ActionObtain prior authorization for listed transplant-related CPT/HCPCS codes and document that the member meets the transplanting institution's eligibility criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

02/01/2002Original effective date

08/05/2026Last review

EnumeratedSelection criteria

PresentExclusions listed

MultipleICD-10 codes

MultipleCPT/HCPCS codes

Coverage Criteria for Hematopoietic Cell Transplantation

Autologous hematopoietic cell transplantation

Covered when ALL of the following are met:

Primary medical necessity for autologous HCT: Member must not have significant co-morbid medical conditions; and the member has adequate major organ function based on the transplanting institution's evaluation; and members with indolent myeloma, smoldering myeloma, and monoclonal gammopathy of uncertain significance (MGUS) are excluded.

Applies to treatment of amyloidosis, multiple myeloma, or POEMS syndrome when the transplanting institution's written eligibility criteria are met.

Second autologous transplant (relapse)

A second autologous HCT may be considered when the following are met:

Second autologous HCT after relapse: Relapse of responsive multiple myeloma (MM) or POEMS syndrome after a durable complete or partial remission following an autologous transplantation; and the second course is not considered a tandem transplantation.

Medical necessity when criteria met.

Policy Summary

PayerAetna

PolicyHematopoietic Cell Transplantation for Multiple Myeloma

Policy CodePolicy 0497

Change TypeNo material change

Effective Date02/01/2002

Last ReviewAug 5, 2026

Next Review Date05/27/2027

Key ActionObtain prior authorization for listed transplant-related CPT/HCPCS codes and document that the member meets the transplanting institution's eligibility criteria.

SourceLink

On This Page

Allogeneic hematopoietic cell transplantation (non‑myeloablative)

Non-myeloablative allogeneic HCT (reduced intensity) is considered medically necessary when:

Reduced intensity allogeneic HCT eligibility: Member is eligible for conventional allografting and meets the transplanting institution's protocol eligibility criteria.

Also considered when protocol eligibility criteria are met for conventional allografting.

Tandem (sequential) transplants

Tandem transplants (autologous→autologous or autologous→allogeneic) are covered when ALL of the following are met:

Tandem transplant selection: Member has active myeloma; and planned first and second transplantation are within a 6-month period; and the member meets the afore‑mentioned general selection criteria (no significant comorbidities and adequate major organ function per the transplanting institution).within 6 months

When autologous followed by allogeneic, donor selection should meet NDMP criteria for unrelated donors when applicable.

Early relapse post-autologous HCT

Covered when BOTH of the following are met (in absence of a protocol):

Relapse after prior autologous HCT: Member has adequate major organ function based upon the transplanting institution's evaluation; and member has early relapse (less than 24 months) after primary therapy that included an autologous hematopoietic cell transplantation (applies to multiple myeloma only).<24 months

Consideration of further transplant requires documentation of early relapse.

Salvage autologous HCT criteria

Expert consensus statements on salvage autologous HCT:

Salvage autologous HCT standard: In transplantation-eligible patients relapsing after primary therapy that did not include an autologous HCT, high‑dose therapy with HCT as part of salvage therapy should be considered standard.

Expert committee consensus.

Salvage autologous HCT after prior autologous HCT: High‑dose therapy and autologous HCT should be considered appropriate for patients relapsing after primary therapy that included an autologous HCT when the initial remission duration was greater than 18 months.>18 months

From expert committee guidance.

Autologous HCT as bridge: High‑dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT.

Allogeneic HCT criteria

Expert consensus statements on allogeneic HCT:

Allogeneic HCT for early relapse/high-risk: Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or for patients with high‑risk features (cytogenetic abnormalities, extramedullary disease, plasma cell leukemia, or elevated LDH).relapse <24 months or high‑risk features

Allo‑HCT should be performed in the context of a clinical trial when possible.

Allogeneic HCT in trials: Allogeneic HCT should be performed in the context of a clinical trial if possible and the role of post‑allogeneic maintenance requires study in prospective trials.

Tandem/double transplant findings

Double/tandem transplant evidence-based findings:

Double vs single transplant outcomes: Randomized data (Attal et al., 2003) demonstrated improved 7‑year event‑free survival and overall survival with double ASCT compared with single ASCT, particularly among patients who did not achieve a very good partial response after one transplant.

Attal et al. randomized trial results.

Tandem evidence from non‑randomized comparisons: Non‑randomized comparisons (Bruno et al., 2007) suggested higher complete remission rates and longer median overall and event‑free survival for autologous followed by allogeneic HCT versus tandem autologous in selected patients with HLA‑identical siblings.

Bruno et al. findings.

Meta‑analysis findings: Pooled randomized trials and meta‑analysis (Kumar et al., 2009) showed no consistent OS or EFS benefit with tandem AHCT overall, despite improved response rates and an increase in treatment‑related mortality.

Kumar meta‑analysis results.

Coverage-relevant evidence and recommendations

Coverage guidance and evidence summary relevant to transplant approaches in multiple myeloma:

Auto‑HCT for newly diagnosed MM: Auto‑HCT consolidation is endorsed as a standard‑of‑care option for patients with newly diagnosed multiple myeloma (ASTCT consensus).

ASTCT RAND‑modified Delphi consensus statements.

Tandem vs single ASCT evidence: Randomized trials report mixed results: some trials (e.g., Attal et al.) reported improved long‑term outcomes with double transplant in selected patients, but pooled RCTs/meta‑analyses did not demonstrate consistent OS/EFS benefit and reported increased treatment‑related mortality with tandem AHCT.

References: Attal et al., Kumar et al. meta‑analysis.

Allogeneic transplant and CAR‑T in frontline: Allogeneic HCT and CAR‑T are not recommended in the frontline setting outside clinical trials per ASTCT recommendations; allo‑HCT in relapsed/refractory MM is encouraged only in clinical trial contexts.

ASTCT recommendations.

Renal impairment considerations: Transplant candidacy should be based on fitness, functional status, frailty, and comorbidity rather than kidney function in isolation; dialysis‑dependent patients can achieve dialysis independence after transplant in many cases.

Guideline and registry data summarized.

Outpatient and bloodless ASCT: Outpatient ASCT is feasible and may be appropriate in selected patients with adequate support; bloodless ASCT has been reported as safe and feasible in retrospective series.

Feasibility and safety evidence summarized.

Sequencing after BCMA‑targeted therapies: Patients previously exposed to anti‑BCMA therapies may respond to cilta‑cel, but existing data are preliminary, sample sizes small, and sequencing strategies require further study; consider clinical‑trial contexts and careful case review.

CARTITUDE‑2 cohort data and authors' cautions.

Members with indolent myeloma, smoldering myeloma, and monoclonal gammopathy of undetermined significance (MGUS) are explicitly excluded from transplant consideration. Exclusion criteria identified in the policy also include inadequate major organ function (for example, cardiac, pulmonary, or hepatic insufficiency), the presence of another life‑limiting cancer or a cancer that could become life‑threatening with immunosuppression, and psychiatric disease that would interfere with the member’s ability to comply with therapy.

Historical series of high‑dose chemotherapy with autologous bone marrow transplant (HDC‑ABMT/ASCT) reported that patients in resistant or refractory relapse had poor outcomes and did not achieve complete remissions, with high early mortality in some cohorts; early investigators therefore concluded HDC‑ABMT was not recommended for resistant relapse in these reports.

Randomized trials comparing single versus tandem ASCT were conducted prior to widespread use of contemporary novel agents; methodological heterogeneity, selection biases, limited integration of modern therapies, and inconsistent survival benefits limit the applicability of these older trials to current practice.

The policy notes that available data describing responses after non‑cellular anti‑BCMA therapies (for example, BCMA‑ADCs or BCMA bispecifics) may not directly inform outcomes following prior anti‑BCMA CAR‑T; the direct relevance is unclear and sequencing decisions require further study.

The referenced additional information and administrative material in the excerpt do not provide further explicit clinical exclusion criteria beyond those noted elsewhere in the policy.

Assessment for circulating plasma cells (CPCs) is mentioned in the policy as a prognostic consideration; CPC evaluation is noted among exclusion/assessment items and documentation of CPC status may be relevant to risk stratification and transplant decision‑making.

Early studies of HDC‑ABMT reported high early mortality and lack of complete remissions among patients with resistant relapse, leading investigators at the time to advise against use of ablative transplant approaches in that subgroup.

Tandem (double) autologous HCT is not supported as a routine approach for all patients because pooled randomized data did not demonstrate consistent overall survival or event‑free survival benefit and showed increased treatment‑related mortality in some analyses; use should be individualized or occur in trial settings.

No additional specific coverage commentary is provided in the supplied administrative excerpt for this placeholder; users are referred to the policy and Clinical Policy Bulletin notes for fuller administrative details.

Coding and Diagnostic Codes

Covered CPT Codes (if selection criteria are met)CPTCovered

38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic.
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous.
38230	Bone marrow harvesting for transplantation.
38232	autologous.
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor.
38241	autologous transplantation.
86813	HLA typing; A, B or C multiple antigens.
86817	DR/DQ, multiple antigens.
86821	lymphocyte culture, mixed (MCL).
38204	Bone Marrow or Stem Cell Services/Procedures (group listing).

1–10 of 14

1/2

Covered HCPCS Codes (if selection criteria are met)HCPCSCovered

S2150

Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic; emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition.

Other related drug/administration codesHCPCS

J9000-J9999	Chemotherapy drugs.
Q0083-Q0085	Chemotherapy administration.

ICD-10 Codes covered if selection criteria are metICD-10Covered

C90.00-C90.02	Multiple myeloma.
C90.10-C90.12	Plasma cell leukemia.
D47.2	Monoclonal gammopathy.
D47.Z9	Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue [POEMS].
E85.0-E85.9	Amyloidosis.

ICD-10 Codes not covered for indications listedICD-10Not Covered

C88.00-C88.01	Waldenstrom macroglobulinemia.
D89.2	Hypergammaglobulinemia, unspecified.
E63.9	Nutritional deficiency, unspecified [additional code required, see I43].
I43	Cardiomyopathy in diseases classified elsewhere [this code is to be used with E63.9].

Diagnostic thresholds and staging values

M-component (serum electrophoresis)Identifiable when concentration is ≥ 0.5 g/dL (serum electrophoresis)

Hemoglobin — Stage I> 10 g/dL (greater than 100 g/L)

Hemoglobin — Stage III< 8.5 g/dL (less than 85 g/L)

Urine light chain (24 hr) — Stage I< 4 g/24 hr

Urine light chain (24 hr) — Stage III> 12 g/24 hr

WBC thresholds — discharge context

WBC discharge parameter (general HDC)WBC greater than 500/mm3 may be acceptable for discharge when other criteria met

WBC discharge parameter (HDC with TBI)WBC greater than 1,000/mm3 required for discharge after high-dose chemotherapy with total body irradiation (TBI)

Fever-free requirement prior to dischargeFever-free for 48 hours off antibiotics (context for WBC-based discharge)

Minimum CD34+ collection

Minimum CD34+ collection target2.0 × 10^6 CD34+ cells/kg (minimum collection threshold)

Achievability after prior radiationReported that 99% of patients achieved this minimum collection threshold even after prior radiation in a cited cohort (Damron et al., 2023)

Mobilization guidance relevanceConsider early stem cell harvest and mobilization strategies (e.g., chemotherapy-based mobilization or plerixafor) to optimize yield when prolonged exposure to agents may reduce collection

Circulating plasma cells threshold

Circulating plasma cells (CPCs) threshold>= 5% circulating plasma cells listed by NCCN as a high‑risk feature

Prognostic significanceElevated CPCs are associated with worse overall survival and progression-free survival in meta-analyses

Detection methodsIdentified by peripheral blood cytology or flow cytometry (multi-parameter flow cytometry often used)

Provider Actions, Authorization, and Documentation

Prior Authorization

Obtain prior authorization for listed transplant procedure and related codes

Prior authorization is required for the transplant-related CPT and HCPCS codes listed in the policy when the medical necessity selection criteria are met; submit PA for the specific procedure codes (e.g., stem cell harvesting, transplantation, HLA typing, chemotherapy administration) included in the policy when requesting coverage.

Covered CPT/HCPCS codes are enumerated in the policy and require authorization when selection criteria are met (see CPT/HCPCS lists).

Prior Authorization

Indicate transplant type and conditioning regimen on authorization

Specify the intended transplant type (autologous vs allogeneic) and the conditioning regimen (for example, high-dose melphalan or HDC with TBI) on authorization requests because expected hospitalization needs and length of stay vary by regimen.

High-dose melphalan (140–200 mg/m2) may be outpatient; regimens including TBI typically require ~30 days hospitalization — document regimen to inform authorization.

Prior Authorization

Request authorizations consistent with recommended sequencing of cellular therapies

When requesting authorization, align timing and sequencing of cellular therapies with clinical recommendations: auto‑HCT is endorsed as frontline consolidation while allo‑HCT and CAR‑T in the frontline setting are recommended only in clinical trials — reflect these sequencing considerations in requests and trial exceptions where applicable.

ASTCT endorses auto‑HCT consolidation for newly diagnosed MM and advises allo‑HCT and CAR‑T in frontline only within clinical trials.

Note

Document sequencing context for BCMA‑targeted therapies; no explicit PA sequencing rules provided

Be aware the policy discusses sequencing of BCMA‑targeted agents (e.g., prior ADC/BsAb exposure before cilta‑cel) but does not establish explicit prior‑authorization or code‑level sequencing rules; include clinical rationale and trial history in the submission when sequencing is relevant.

CARTITUDE‑2 data show responses after prior non‑cellular anti‑BCMA exposure, but sample sizes and prior‑treatment details were limited — document prior BCMA therapies and timing.

Prior Authorization

Follow plan resources for prior‑authorization submission details

The policy excerpt does not provide detailed plan-specific prior authorization procedures or forms; consult the plan’s Clinical Policy Bulletin Notes and other plan resources for submission instructions and PA contact information.

Users are directed to Clinical Policy Bulletin Notes and plan resources for administrative PA details.

Step Therapy

No step‑therapy algorithm specified in this excerpt

No formal step‑therapy sequencing is specified in this portion of the policy; the policy states that step therapy is not applicable here.

When considering sequencing of therapies (including cellular therapies), the policy provides clinical guidance but does not mandate a step‑therapy algorithm.

Step Therapy

Consider salvage autologous HCT per expert consensus criteria

Salvage autologous HCT should be considered for transplantation‑eligible patients who relapse after primary therapy that did not include an autologous HCT, and for patients who relapsed after prior autologous HCT if the initial remission duration was greater than 18 months.

Expert consensus: salvage autologous HCT is standard for transplant‑eligible patients relapsing after non‑ASCT primary therapy.
Salvage autologous HCT appropriate when prior autologous HCT remission duration >18 months.

Note

Provider guidance placeholder — consult policy citations

No additional provider‑action text is specified in the excerpt for this placeholder; refer to the policy and cited references for further clinical guidance as needed.

Note

Documentation Required

Submit documentation that member meets transplant center eligibility criteria

Document that the member meets the transplanting institution’s written eligibility or protocol criteria, including adequate major organ function and absence of significant comorbid conditions; when applicable, document early relapse timing (<24 months) after prior autologous HCT.

Selection criteria include absence of significant comorbidities and adequate major organ function per transplant center evaluation.
Early relapse (<24 months) after prior autologous HCT must be documented when applicable.

Documentation Required

Document stem cell mobilization and collection details (apheresis, regimen, yields)

Include detailed documentation of stem cell mobilization and collection procedures in the record and authorization submission — note use of apheresis catheter placement, number of apheresis procedures (typically 5–10), mobilization regimen (e.g., cyclophosphamide and/or GM‑CSF), and collected yields.

Apheresis catheter insertion and number of outpatient apheresis procedures should be recorded.
Mobilization protocols and whether inpatient hospitalization was required (e.g., high‑dose cyclophosphamide) should be documented.

Documentation Required

Provide pre‑transplant fitness, frailty, comorbidity, and renal function documentation

Provide pre‑transplant clinical documentation of patient fitness, functional status, frailty assessment, comorbidity profile, and renal function (including dialysis dependence when applicable) to support candidacy and expected outcomes.

Guidelines recommend assessing candidacy based on fitness/frailty/comorbidity rather than kidney function alone; document dialysis status and prior hematologic response if combined kidney transplant considered.

Documentation Required

Document prior BCMA therapies and circulating plasma cell status for sequencing and risk assessment

When sequencing therapies or considering cellular therapies after BCMA‑targeted agents, document prior BCMA‑targeted therapies and timing; record presence or absence of circulating plasma cells (CPCs), since CPCs ≥5% are identified as a high‑risk feature relevant to risk stratification.

Document prior exposure to ADCs, BsAbs, CAR‑T, including dates and response when available.
Record CPC assessment (threshold ≥5% flagged by NCCN) to inform risk and sequencing decisions.

Documentation Required

No further documentation specifics in this excerpt — use plan resources for forms

This excerpt does not list additional specific documentation requirements beyond those above; consult the full Clinical Policy Bulletin Notes and plan resources for any plan‑specific forms or checklists.

Policy provides links to additional information and glossary; use plan resources for administrative documentation requirements.

Denial Risk

Recognize exclusion conditions that may lead to denial — confirm organ function and compliance

Transplant requests may be denied when members have inadequate cardiac, pulmonary, or hepatic function, another life‑limiting cancer or a cancer that may become life‑threatening with immunosuppression, or psychiatric disease that would interfere with compliance; verify and document organ function and comorbidity status to avoid denial.

Exclusion criteria listed include inadequate cardiac, pulmonary, or hepatic function and psychiatric disease that impairs compliance.
Presence of another life‑limiting cancer that could worsen with immunosuppression is an exclusion.

Denial Risk

Document and address historical adverse risk factors that could affect authorization

Be alert that historically identified adverse risk factors — including high transplant‑related mortality, inadequate organ function, and heavy prior therapy — were associated with worse outcomes and may influence eligibility decisions; document how the patient’s risk profile differs from historical exclusion criteria.

Trials historically excluded patients with inadequate cardiac, renal, pulmonary, or hepatic function or with heavy prior therapy.

Denial Risk

Justify tandem transplant requests with selection criteria or trial context due to TRM and mixed evidence

Tandem (double) autologous transplantation may increase treatment‑related mortality and has inconsistent evidence for survival benefit across pooled randomized trials; when requesting tandem transplants, document specific clinical indications, trial participation, or selection criteria that justify tandem strategy.

Attal et al. showed benefit in selected patients, but meta-analysis found no consistent OS/EFS benefit and increased TRM with tandem AHCT — provide selection rationale.

Note

Background material does not list explicit authorization/denial triggers — support requests with required documentation

No explicit authorization or denial triggers are provided in these background chunks; interpret clinical recommendations in the policy and support authorization requests with the documentation described herein.

Background sections summarize evidence and recommendations but do not list additional administrative triggers.

Note

Policy excerpt informational — follow plan procedures for coverage decisions

This excerpt does not specify any additional provider actions; note the Clinical Policy Bulletin is informational and users should follow plan procedures for benefit determination.

Aetna Clinical Policy Bulletins assist in administering benefits but do not replace clinical judgment or plan‑specific administrative rules.

Conditioning, Mobilization, and Regimen Options

Regimen	Details	Coverage stance
High-dose melphalan
Melphalan dosing range 140–200 mg/m2 administered as conditioning for autologous HCT; may be given outpatient in some settings with home hydration; other HDC regimens (e.g., EDAP) generally require hospitalization
Covered with criteria

Strategy	Evidence/notes	Coverage stance
Tandem (sequential) autologous ASCTs
Randomized and controlled trials (e.g., Attal et al.) showed improved long-term EFS and OS with double ASCT versus single ASCT in selected patients, particularly those without a very good PR after one transplant
Covered with selection criteria/trial context

Comparison	Study details	Coverage stance
Autologous → reduced-intensity allogeneic vs tandem autologous
Bruno et al: melphalan 200 mg/m2 before autologous transplant then non‑myeloablative TBI prior to allogeneic transplant vs tandem autologous with melphalan before each transplant; higher CR rates and longer median OS/EFS in allo group but differing conditioning regimens and GVHD risk noted
Neutral/informational; individual consideration required

Regimen comparison	Trial details	Coverage stance
Single ASCT followed by maintenance vs tandem ASCT
Abdelkefi et al: randomized trial of tandem upfront transplant (arm A) versus single ASCT followed by thalidomide maintenance (arm B); at median follow-up 33 months, 3‑year OS and PFS favored single ASCT plus thalidomide maintenance
Neutral/informational; may be considered per trial context

Therapy	Clinical context and outcomes	Coverage stance
Ciltacabtagene autoleucel (cilta-cel) — single infusion after lymphodepletion
CARTITUDE‑2 cohort C: salvage cilta‑cel given to patients progressed after PI, IMiD, anti‑CD38 antibody and non‑cellular anti‑BCMA therapy; 20 patients treated, ORR 60%, MRD negativity 35% (MRD‑evaluable 70%); CRS common (60%) with mostly grade 1–2
Informational for salvage, consider in later-line/refractory settings; sequencing after prior anti‑BCMA requires case-level review

Regimen / strategy	Notes / references	Coverage stance
Bortezomib-containing induction and proteasome inhibitor–based maintenance
References include NCCN and randomized/registry studies supporting bortezomib induction prior to ASCT and PI‑based maintenance after transplant (see cited references)
Covered per guideline-aligned practice when selection criteria met

Line-of-Therapy Context

salvage

Salvage (line-of-therapy) top-level criteria:

Indications: Used for treatment of amyloidosis, multiple myeloma, or POEMS when transplant eligibility or protocol criteria are met; salvage autologous HCT is appropriate for transplantation‑eligible patients relapsing after primary therapy that did not include autologous HCT, and for relapsed patients with initial remission >18 months after prior autologous HCT.remission >18 months when prior autologous HCT

Expert consensus statements support these salvage indications.

first-line

First‑line transplant context (top-level node):

Initial/autologous consolidation: High‑dose chemotherapy with autologous HCT is an option for newly diagnosed, transplantation‑eligible patients as consolidation; early versus delayed ASCT yields comparable overall survival in some cohorts when early stem cell collection is performed.

Kumar et al. and ASTCT consensus support auto‑HCT as a standard‑of‑care consolidation option.

salvage

Salvage (alternate reference) top-level node:

Salvage autologous HCT criteria: Appropriate for relapsed patients who are transplantation‑eligible and meet remission‑duration criteria (e.g., >18 months after prior autologous HCT) or when primary therapy did not include autologous HCT.>18 months

Expert committee consensus statements.

first-line

First‑line node referenced in guideline/evidence section:

Frontline consolidation: Auto‑HCT is recommended as a standard‑of‑care consolidation option for newly diagnosed multiple myeloma in transplantation‑eligible patients (ASTCT consensus).

RAND‑modified Delphi panel recommendations.

salvage

Salvage node referenced in guideline/evidence section:

Salvage indication: Salvage autologous HCT is standard for patients relapsing after primary therapy that did not include autologous HCT and is appropriate for relapsed patients with initial remission duration >18 months following prior autologous HCT.>18 months

Expert consensus guidance encourages collection of stem cells sufficient for two transplants early in the disease course.

salvage

Salvage node referenced regarding sequencing and CAR‑T context:

Salvage/late‑line context: CARTITUDE‑2 cohort C included patients who progressed after proteasome inhibitor, immunomodulatory drug, anti‑CD38 antibody, and non‑cellular anti‑BCMA immunotherapy; cilta‑cel was used as later‑line therapy and showed responses but data are preliminary and sequencing strategies require further study.

CARTITUDE‑2 cohort data; authors advise cautious interpretation due to small sample size and heterogeneity of prior therapies.

Biomarkers and Risk Features

Cytogenetics — risk information

Cytogenetics — roleCytogenetic abnormalities are considered a high‑risk feature and inform consideration of allogeneic HCT in early relapse or high‑risk disease

Context for useUsed with other high‑risk features (extramedullary disease, plasma cell leukemia, high LDH) to guide transplant strategy

Recommendation settingAllogeneic HCT in presence of high‑risk cytogenetics should preferably be performed in a clinical trial when possible

LDH — risk marker

LDH — risk markerHigh lactate dehydrogenase (LDH) is identified as a high‑risk feature relevant to consideration of allogeneic HCT

Clinical implicationElevated LDH contributes to categorization of early relapse/high‑risk disease that may prompt allogeneic transplant evaluation

Use in risk stratificationConsider LDH alongside cytogenetics and clinical features when assessing transplant strategy

Circulating plasma cells (CPCs)

CPCs threshold (repeat)>= 5% circulating plasma cells designated as high‑risk by NCCN

Prognostic evidenceMeta-analyses show CPC positivity associates with poorer OS and PFS and the adverse impact is not eliminated by ASCT

Detection and reportingMeasured via peripheral blood cytology or flow cytometry; cutoffs and method-specific thresholds noted in literature

Definitions

Tandem transplant

Tandem transplant — conceptSequential transplantation strategy using an initial autologous transplant followed by a second cycle (often another autologous transplant) typically about 6 months later to attempt deeper or more durable responses

TimingPlanned first and second transplantations should be within a 6‑month period when performed as tandem transplants

VariantsMay include autologous→autologous or autologous→allogeneic sequencing depending on donor availability and protocol

Autologous HCT — definition

Autologous HCT — definitionHematopoietic cell transplantation using the patient's own harvested marrow or peripheral stem cells to permit marrow‑ablative chemotherapy dosing and subsequent marrow rescue

PurposeEnables use of myeloablative doses of chemotherapy to increase tumor cell kill while permitting hematopoietic recovery via reinfusion of harvested cells

Typical componentsInvolves stem cell harvest (bone marrow or peripheral), preservation, high‑dose chemotherapy conditioning, and reinfusion

Non-myeloablative allogeneic HCT

Non‑myeloablative allogeneic HCT — definitionReduced‑intensity (mini‑) allogeneic transplant intended to provide graft‑versus‑tumor effect with lower immediate toxicity than conventional myeloablative allograft

IndicationConsidered medically necessary for eligible patients with MM or POEMS when they meet conventional allografting eligibility or protocol criteria

Recommendation contextAllogeneic HCT is recommended preferably in the context of a clinical trial when possible

ABMT / ASCT — definition

ABMT / ASCT — definitionAutologous bone marrow transplant (ABMT) or autologous stem cell transplant (ASCT) uses the patient's own harvested marrow or peripheral stem cells to rescue marrow after myeloablative therapy

Procedure stepsMarrow or peripheral stem cell harvest, preservation, high‑dose chemotherapy conditioning, then reinfusion for hematopoietic rescue

Clinical rationaleAllows higher chemotherapy dosing to increase tumor cell kill while providing stem cell support to restore hematopoiesis

Allogeneic BMT / allogeneic HCT — definition

Allogeneic BMT / allogeneic HCT — definitionTransplant using hematopoietic stem cells from a healthy donor to restore marrow function after high‑dose chemotherapy, offering potential graft‑versus‑tumor effect and absence of tumor contamination

Donor typesMay use HLA‑identical sibling, haploidentical, or well‑matched unrelated donor meeting NDMP criteria when applicable

ConsiderationsAssociated with greater potential for graft‑versus‑tumor benefit but higher graft‑versus‑host and transplant‑related toxicity compared with autologous HCT

Tandem (double) transplant

Tandem (double) transplant — definitionSequential high‑dose chemotherapy with ASCT followed by a second HDC/ASCT (or HDC plus TBI and ASCT) typically about 6 months later to attempt deeper responses

PurposeAimed to escalate conditioning dose and improve depth/duration of response compared with single transplant

Evidence caveatRandomized and pooled trials show mixed benefits for OS/EFS and increased TRM in some analyses — patient selection important

Tandem (double) ASCT

Tandem (double) ASCT — definitionTwo successive autologous stem cell transplants performed as part of first‑line therapy for multiple myeloma

Clinical contextMay improve long‑term outcomes in selected patients (e.g., those not achieving very good partial response after one transplant) per randomized data

Selection importanceNot routinely supported for all patients due to heterogeneity in trial results and increased TRM; use individualized or within trials

Autologous followed by allogeneic transplant

Autologous followed by allogeneic transplant — conceptStrategy using an initial autologous transplant followed later by an allogeneic transplant from an HLA‑identical sibling (sometimes reduced‑intensity conditioning) to combine cytoreduction with graft‑versus‑tumor effect

Comparative findingsNon‑randomized data showed higher CR rates and longer median OS/EFS with autologous→allogeneic versus tandem autologous in selected patients (Bruno et al.)

ApplicabilityOften limited to patients with HLA‑identical sibling donors and may be best studied in clinical‑trial settings

cilta-cel

cilta‑cel — definitionCiltacabtagene autoleucel (cilta‑cel) is an anti‑BCMA chimeric antigen receptor T‑cell therapy evaluated in CARTITUDE‑2 and other cohorts

Administration formatSingle infusion following lymphodepletion (as in CARTITUDE‑2 cohort C)

Clinical contextUsed as later‑line salvage therapy in patients previously exposed to proteasome inhibitors, IMiDs, anti‑CD38, and non‑cellular anti‑BCMA therapies in cited cohorts

circulating plasma cells (CPCs)

Circulating plasma cells (CPCs) — definitionPeripheral blood clonal plasma cells detected by cytology or flow cytometry, associated with prognosis and disease dissemination in MM

Prognostic impactMeta‑analyses demonstrate CPC positivity is associated with worse OS and PFS, and adverse impact may persist despite ASCT

Risk stratification useNCCN lists CPCs ≥5% as a high‑risk feature relevant to prognosis and transplant decision‑making

Definitions and Review History links note

Definitions and Review History linksDefinitions and Review History links are provided in the policy (external links referenced in the document); full definitions content not included in excerpt

Policy review datesLast review: 08/05/2026; Effective: 02/01/2002; Next review: 05/27/2027

Access noteSee policy web page for full Definitions and Review History details

Background and Evidence Context

Multiple myeloma is a clonal plasma cell malignancy characterized by a measurable monoclonal immunoglobulin (M‑component) and clinical features such as lytic bone lesions, hypercalcemia, anemia, renal dysfunction, and increased risk of infection. High‑dose chemotherapy with autologous or allogeneic hematopoietic cell transplantation is an option for transplantation‑eligible patients who meet institutional eligibility criteria and do not have prohibitive comorbidities.

Revision History

2026-08-05policy_reviewLatest

Policy last reviewed and updated header/footer; next scheduled review listed.

2002-02-01effective_date

Original policy effective date established.