Latest Review Date: May 2024

Category: Surgery                                  

POLICY

Injection of allograft into the intervertebral disc for the treatment of degenerative disc disease is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE

Degeneration of the intervertebral discs is commonly observed in imaging and has been proposed to be a source of back pain. In order to treat the observed changes in the discs, cellular therapies such as mesencyhmal stem cells are being studied. One of these cellular therapies involves the intradiscal injection of a mixture of nucleus pulposus allograft and viable cells into the degenerated disc.

Degenerative Disc Disease

Back pain is a common condition in adults. Most episodes of back pain are self-limited and will resolve within 1 month, but a small percentage will persist and become chronic. Chronic back pain can arise from a variety of etiologies including musculoskeletal pain, vertebral compression fractures, spinal stenosis, disc herniation, or other degenerative changes to the disc that compress the nerve roots and lead to radiculopathy. Age-related degeneration of the intervertebral discs is common and includes numerous biochemical and morphologic changes; the most common of which is loss of glycosaminoglycan and associated loss in water content. Pro-inflammatory molecules increase, while endplate calcification impairs, nutrient flow. Together, these lead to an increase in cell death in the nucleus pulposus. Although degenerative changes to the disc are frequently observed on imaging, their contribution to back pain in the absence of radiculopathy is uncertain. Spine imaging, such as magnetic resonance imaging, computed tomography, or plain radiography, shows that lumbar disc degeneration is widespread, but for most people does not cause symptoms. Because many degenerative changes of the disc that are seen on imaging are asymptomatic, identifying the source of the back pain is challenging.

Treatment

Conservative management of back pain is the first-line treatment for most patients. Nonsteroidal anti-inflammatory drugs or other analgesics are used for symptom relief. Duloxetine or tramadol are recommended second-line pharmacologic therapies by the American College of Physicians. Additionally, modification of activity in conjunction with some form of exercise therapy is frequently prescribed early in the course of symptoms. For patients with persistent nonradicular back pain, guidelines recommend interdisciplinary rehabilitation, which is defined as an integrated approach using physical rehabilitation in conjunction with a psychological or psychosocial intervention. Opioids may also be prescribed. Although spinal fusion surgery is frequently performed for non-specific back pain with degenerative changes to the disc, surgery has not been shown to be more effective than comprehensive conservative treatment. Cell therapy is being explored as a method to regenerate the intervertebral disc by rehydration, height restoration, and repopulating native cells.

KEY POINTS

This evidence review was created in May 2021 with a search of the PubMed database. The most recent literature update was performed through April 9, 2024.

Summary of Evidence

For individuals with degenerative disc disease who receive a viable allograft injection, the evidence includes 12-month results from an RCT. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Results from the first 12 months of the planned 36 months of follow-up did not find statistically significant differences between the active allograft, placebo allograft, and conservative management groups on the co-primary pain and disability endpoints. However, the proportion of treatment responders was significantly greater in the active allograft group on some, but not all pain and disability response outcomes. Given the various important comparator and outcome relevance, data completeness, and power limitations, evidence from well-conducted trials demonstrating consistent improvements in health outcomes is still needed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American College of Physicians

In 2017, the American College of Physicians recommended that "For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation. (Grade: strong recommendation, low-quality evidence).

In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence)."

North American Spine Society et al

In 2020, the North American Spine Society, along with 9 other societies, published multidisciplinary evidence-based guidelines on the diagnosis and treatment of low back pain. There were 82 clinical questions that were addressed in the comprehensive evidence review. Regarding degenerative disc disease, the guideline gave a grade A recommendation that provocative discography without manometric measurements correlates with both pain reproduction in the presence of moderate to severe disc degeneration on MRI/CT [magnetic resonance imaging/computed tomography] discography and with the presence of endplate abnormalities on MRI imaging. There was insufficient evidence to make a recommendation for or against the use of intradiscal bone marrow concentrate in patients with discogenic low back pain, and no review of intradiscal allograft injection.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS

Degenerative Disc Disease, DDD, allograft injections, VIA Disc Matrix, rexlemestrocel-L, mesenchymal precursor cell (MPC) therapy

APPROVED BY GOVERNING BODIES

VIA Disc Matrix (Vivex Biomedical) is composed of human disc tissue donated from cadavers with viable cells. It consists of a nucleus pulposus allograft suspension that is mixed with a minimum of 6 X106 cryopreserved cells. The cell source and method of processing has not been disclosed, and it is not clear if VIA Disc Matrix meets the U.S. Food and Drug Administration (FDA) criteria for what is considered minimal manipulation and homologous use for human cells, tissues, and cellular and tissue-based products (HCT/Ps).

The FDA regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation, Title 21, parts 1270 and 1271. In 2017, the FDA published clarification of HCT/Ps which was updated in 2020.

HCT/Ps are defined as human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient. If a HCT/P does not meet the criteria below and does not qualify for any of the stated exceptions, the HCT/P will be regulated as a drug, device, and/or biological product and applicable regulations and premarket review will be required.

An HCT/P is regulated solely under section 361 of the Public Health Service (PHS) Act and Title 21 Code of Federal Regulations (CFR) Part 1271 if it meets all of the following criteria:

1. "The HCT/P is minimally manipulated;
2. The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent;
3. The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and
4. Either:
   1. The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
   2. The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
      1. Is for autologous use;
      2. Is for allogeneic use in a first-degree or second-degree blood relative; or
      3. Is for reproductive use"

Rexlemestrocel-L (MPC-06-ID, Mesoblast) is an allogeneic mesenchymal precursor cell (MPC) therapy under investigation for the treatment of chronic low back pain caused by disc degeneration in individuals "who have exhausted conservative treatment options, may have failed epidural steroid injections and have no further treatment option other than invasive and costly surgical intervention." Amirdelfan et al (2021) published results of a multicenter, randomized, controlled study of rexlemestrocel-L in 100 individuals with degenerative disc disease (NCT01290367). Additionally, in July of 2021, Mesoblast completed a larger Phase 3 randomized, double-blind, placebo-controlled trial of rexlemestrocel-L in 404 individuals with degenerative disc disease with 36 months of follow-up (NCT02412735). Although this trial is not yet published, it has been reviewed by FDA's Office of Tissues and Advanced Therapies (OTAT). Based on FDA OTAT feedback, as part of their market approval application, Mesoblast plans to conduct an additional US Phase 3 trial with pain reduction at 12 months as the primary endpoint.

BENEFIT APPLICATION

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING 

CPT codes     

REFERENCES

1. Amirdelfan K, Bae H, McJunkin T, et al. Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy. Spine J. Feb 2021; 21(2): 212-230. 
2. Beall DP, Davis T, DePalma MJ, et al. Viable Disc Tissue Allograft Supplementation; One- and Two-level Treatment of Degenerated Intervertebral Discs in Patients with Chronic Discogenic Low Back Pain: One Year Results of the VAST Randomized Controlled Trial. Pain Physician. Sep 2021; 24(6): 465-477.
3. Beall DP, Wilson GL, Bishop R, et al. VAST Clinical Trial: Safely Supplementing Tissue Lost to Degenerative Disc Disease. Int J Spine Surg. Apr 2020; 14(2): 239-253.
4. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
5. Katz NP, Paillard FC, Ekman E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surg Res. Feb 03 2015; 10: 24.
6. Mesoblast.Chronic  Low  Back  Pain  Due  to  Disc  Degeneration.  2022.  www.mesoblast.com/product-candidates/spine-orthopedic-disorders/chronic-discogenic-low-back-pain
7. Mesoblast. Single Dose of Mesoblast's Allogeneic Cell Therapy Provides Durable Pain Reduction for At Least Three Yearsin Patients with Degenerative Disc Disease: Global Newswire. January 11, 2022. www.globenewswire.com/news-release/2022/01/12/2365313/0/en/Single-Dose-of-Mesoblast-s-Allogeneic-Cell-Therapy-Provides-Durable-Pain-Reduction-for-at-Least-Three-Years-in-Patients-With-Degenerative-Disc-Disease.html
8. North American Spine Society. Evidence-based clinical guidelines for multidisciplinary spine care: Diagnosis and treatment of low back pain. 2020. https://www.spine.org/Portals/0/assets/downloads/ResearchClinicalCare/Guidelines/LowBackPain.pdf.
9. Parker SL, Mendenhall SK, Shau DN, et al. Minimum clinically important difference in pain, disability, and quality of life after neural decompression and fusion for same-level recurrent lumbar stenosis: understanding clinical versus statistical significance. J Neurosurg Spine. May 2012; 16(5): 471-8.
10. Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. Apr 04 2017; 166(7): 514-530.
11. U.S. Food and Drug Administration. Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use Guidance for Industry and Food and Drug Administration Staff. 2017 www.regulations.gov/document?D=FDA-2017-D-6146-0003

POLICY HISTORY

Medical Policy Panel, May 2021

Medical Policy Group, July 2021 (7): New Policy addressing existing investigational technology. Available for comment July 7, 2021 through August 21, 2021.

Medical Policy Panel, May 2022

Medical Policy Group, May 2022 (7): Update to Key Points, Approved by Governing Bodies, and References. Added Key Words: “rexlemestrocel-L, mesenchymal precursor cell (MPC) therapy.” No change in Policy Statement.

Medical Policy Panel, May 2023

Medical Policy Group, July 2023 (7): Updates to Key Points, Benefit Application, and References. No change to Policy Statement.

Medical Policy Panel, May 2024

Medical Policy Group, May 2024 (7): Updates to Key Points, Approved by Governing Bodies, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.