JUNE 16, 2014
Gap in Herpes, VTE Prevention Seen in Myeloma
At HOPA Annual Conference...

New Orleans—Not all patients with multiple myeloma (MM) are receiving prophylaxis in accordance with the National Comprehensive Cancer Network guidelines, making them prone to higher rates of herpes zoster and venous thromboembolism, according to data presented at the 2014 Annual Conference of the Hematology/Oncology Pharmacy Association (HOPA).

In a study of patients with MM or mantle cell lymphoma (MCL) treated with proteasome inhibitors at the Karmanos Cancer Center, in Detroit, 29% of the 83 patients were not receiving antiviral prophylaxis for herpes zoster (poster 117). The National Comprehensive Cancer Network Guidelines (NCCN) recommend herpes zoster prophylaxis, without suggesting a specific dosing regimen, for patients treated with the proteasome inhibitors bortezomib (Velcade, Millennium) or carfilzomib (Kyprolis, Onyx). The guidelines list both acyclovir and valacyclovir as options to prevent herpes.

The NCCN recommendation is based on evidence from several studies identifying a need for precautionary measures when these drugs are used. In one study, the prevalence of herpes zoster was 13% in patients with MM who were being treated with bortezomib (J Clin Oncol 2008;26:4784-4790). In another report, the prevalence of herpes was 10.3% in patients with MCL or indolent B-cell lymphoma receiving chemotherapy, including bortezomib (Leuk Lymphoma 2013;54:2185-2189).

Retrospective Chart Review

In the Karmanos Cancer Center study, clinicians conducted a retrospective chart review of patients with MM or MCL receiving bortezomib or carfilzomib at the infusion center from January 2012 through July 2013. Among 83 patients, 71% received the recommended prophylaxis and 29% did not. The rate of herpes zoster was significantly higher in patients who did not receive prophylaxis (25% vs. 6.8%; P=0.03).

“I was surprised that 29% of the study population was not receiving antiviral prophylaxis,” said lead author of the study Che Min Chang, PharmD, an oncology pharmacy resident at Karmanos Cancer Center. “Our study shows opportunities for pharmacists to play a role in improving medication compliance. Hospitals can ensure higher adherence to antiviral prophylaxis with patient education and medication reconciliation during clinic visits. Also, the addition of reminders into a paper or electronic chemotherapy order template may help physicians with ordering [of] the medication.”

VTE Prevention

In a second study presented at the HOPA meeting, investigators from University of Cincinnati Medical Center found that few patients with MM who are at increased risk for VTE are receiving the recommended prophylactic therapy to avoid this side effect (poster 7).

Patients with MM have an increased incidence of VTE; the risk is heightened when patients are on immunomodulatory drugs. Studies have shown that when thromboprophylaxis is not used, VTE affects 26% to 75% of newly diagnosed and 11% to 15% of relapsed/refractory patients with MM (Blood 2006;108:403; N Engl J Med 2007;357:2123-2132).

The University of Cincinnati investigators retrospectively studied 62 patients with MM who were receiving immunomodulatory drugs at the medical center and found that 33.9% were given the recommended prophylactic VTE therapy, per the NCCN guidelines (Table).

Table. Risk Assessment Model for Managing VTE In MM Patients Treated With Immunomodulators
Risk Factors
Individual risk factors
  • Obesity (BMI ≥30 kg/m2)
  • Previous VTE
  • CVAD or pacemaker
  • Cardiac disease
  • Chronic renal disease (CrCl <30 mL/min)
  • Diabetes
  • Acute infection
  • Immobilization
  • Surgery
  • General surgery
  • Anesthesia
  • Trauma
  • Use of erythropoietin-stimulating agents
  • Blood-clotting disorders
MM-related risk factors
  • Diagnosis of myeloma
  • Hyperviscosity
MM therapy
  • Thalidomide or lenalidomide in combination with dexamethasone
  • (≥480 mg/mo), doxorubicin, multiagent chemotherapy
Recommended Action
No risk factor or one individual/MM risk factor
  • Aspirin 81-325 mg once daily
  • 2 individual/MM risk factors and/or receiving MM therapy
  • LMWH (equivalent of enoxaparin 40 mg once daily) or full-dose warfarin (target INR 2-3)
BMI, body mass index; CrCl, creatinine clearance; CVAD, central venous access device; INR, international normalized ratio; LMWH, low-molecular-weight heparin; MM, multiple myeloma; VTE, venous thromboembolism

The investigators, led by Ruth Dede, PharmD, an oncology pharmacy resident at the medical center, also found that the risk for developing a VTE was more than double when patients did not receive the NCCN-recommended VTE preventive care. Among patients who received the NCCN-recommended prophylaxis, 4.8% developed a VTE, whereas among those who did not receive the appropriate prophylaxis, 12.2% developed a VTE. The small sample size prevented this difference from being statistically significant, but Dr. Dede said the study results should still spur changes at her institution.

“I plan to present my findings to the physicians who care for these patients,” Dr. Dede said in an interview with Pharmacy Practice News. Moreover, “I hope to develop a best practice advisory [to incorporate] into the computer physician order entry system.”

More Aggressive Care Needed

Jessica Poirier Duda, PharmD, BCOP, a clinical specialist pharmacist in hematology/oncology at the Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University, in Columbus, said she was not surprised by the results of either study because other investigators have documented poor adherence to guideline therapy.

“Both studies confirm the need for appropriate supportive-care medications while patients are on specific chemotherapy agents, such as aspirin for immunomodulatory agents and acyclovir for proteasome inhibitors,” Dr. Duda commented. She added that the studies confirm the risks for certain significant adverse drug events when appropriate prophylaxis is not used.

Beyond that, “there are two important take-away points,” Dr. Duda said. “One, there is still an important need for pharmacist interventions to make sure patients are prescribed appropriate prophylaxis. There are many potential interventions to improve adherence, such as the development of chemotherapy treatment plans, medication reconciliation with chemotherapy, and nursing and provider in-services. Second, we have a unique opportunity to educate patients on these supportive therapies, so they understand the importance of why they need to take the medications to improve adherence.” For example, she said, there is a difference between telling patients they need to start acyclovir while on bortezomib, and explaining the risk for shingles with bortezomib and the importance of taking acyclovir as prescribed.

Overall, Dr. Duda said, the studies underscore the importance of active involvement of pharmacists to ensure safe and appropriate delivery of chemotherapy.

Drs. Chang, Dede and Duda reported no relevant financial conflicts of interest.

Improving Adherence to Evidence-Based Guidelines for Cancer

New Orleans—Various studies have demonstrated that many cancer patients do not receive therapy recommended in guidelines, such as those from the National Comprehensive Cancer Network. A new study reveals that implementation of an oncology prior authorization system through a Web-based portal can increase the use of evidence-based clinical pathway treatment plans by roughly 15%.

“Providers and payors are both increasingly collaborating to improve outcomes and reduce costs and treatment variation. One of the solutions that has been successfully used is the adoption of clinical pathways,” said Barry Peterson, PharmD, BCOP, BCPS, an informatics/pharmacoeconomic specialist at New Century Health (NCH), Brea, Calif., who presented the study during the 2014 Hematology/Oncology Pharmacy Association (HOPA) annual conference.

NCH implemented the chemotherapy prior authorization system at a midwestern oncology network that includes about 60,000 insured members. Using this system, physicians submit their chemotherapy treatment request through an online portal. If the request doesn’t meet evidence-based guidelines, it is flagged for review by an NCH oncologist, who then calls the prescribing physician.

The study compared treatment plan adherence to evidence-based clinical pathways and compendia recommendations before and after the initiation of the prior authorization system. Clinicians focused on compendium adherence rates for treatment of breast, colon, prostate and lung cancers, as well as lymphoma and multiple myeloma. The on-compendium rate was defined as the number of chemotherapy treatment requests reviewed that complied with Centers for Medicare & Medicaid Services–approved compendia, divided by the total chemotherapy requests reviewed.

At baseline, the first quarter of 2011, the on-compendium rate was 82.6%. During the review period, the second quarter of 2011 to the fourth quarter of 2012, adherence jumped to 91.8% (P=0.021). “In quarter 4 of 2012, we had 118 chemotherapy requests, of which 115 met guideline-baseline therapy; so now, we are up to about 97.5%,” Dr. Peterson said.

Bruce A. Feinberg, DO, the vice president and the chief medical officer at Cardinal Health Specialty Solutions, in Dublin, Ohio, has more than 30 years working as a community oncologist and almost two decades working specifically with clinical pathways. He said many factors affect physician compliance with clinical pathways. “User-friendly technology—especially technology that removes or reduces administrative burdens, like prior authorization—is definitely one of those factors.”

An array of additional factors contributes to compliance with guidelines, Dr. Feinberg said, noting that “the most significant factors that contribute to high rates of compliance, are respect for the physician–patient relationship, direct physician engagement in pathway design, true provider–payor collaboration that aligns incentives, compliance thresholds that permit autonomy and individualized patient care.”


Drs. Peterson and Feinberg reported no relevant financial conflicts of interest.

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