Multiple Myeloma, Stem Cell Transplants and ...Shingles

One in three people in the US will have to deal with a case of shingles in their lifetime. It is, most likely, safe to say that anyone of us know the misery that comes with shingles either from first-hand experience or from stories we have heard from family members or friends. Shingles is a painful rash illness resulting from reactivation of varicella zoster virus, the same virus that presents itself as chickenpox in children. The official medical name for shingles in Herpes Zoster (HZ). A recent article in the Journal Clinical Infectious Diseases builds upon research published in 2018 that patients with certain types of cancers are at higher risk of developing shingles than those without cancer.

The authors of the first article referenced above state:

‘Increasing HZ incidence with age has been well defined, however, the risk for HZ conferred by immunocompromising conditions or immunosuppressive drugs has not been as well defined. Immunosuppression is also known to increase the incidence of HZ complications and disease severity.  The most common HZ complication is postherpetic neuralgia (PHN), a painful, persistent condition that can substantially affect quality-of-life among the aged, and has been shown to be more common among immunosuppressed patients’ [emphasis added]

A team of researchers from the US Centers of Disease Control (CDC), and several US universities/cancer centers embarked on a comprehensive literature search starting with 3,765 scientific/medical articles ‘to estimate HZ risk in five categories of immunocompromised patients.’ (stem cell transplant, hematological and solid tumor cancers, HIV and solid organ transplants). Their summary findings should be of interest to every myeloma and stem cell transplant patient :

• ‘The 6 highest estimates of cumulative incidence [of shingles] were reported in HCT [stem cell] recipients. [emphasis added] Among HCT recipients, the risk varied by transplant type : cumulative incidence estimates [of HZ] for autologous HCT is a median of 18.6% and [for] … allogeneic HCT a median of 9 %. All estimates for hematological malignancies, solid tumors, and HIV were below 10%, but estimates varied within the immunocompromising category.’
• The incidence rate of shingles in stem cell recipients is almost 3 times higher compared to what is seen in solid tumor cancer or HIV patients.
• The risk of developing post-herpetic pain lasting more than 90 days [emphasis added] in stem cell recipients ranges between 6 to 41 %, with several studies reporting around 10 %.

The high incidence rates of shingles and post-herpetic pain in the SCT patient population raise the question of what can be done to avoid the associated misery. Prophylaxis with antiviral drugs (such as acyclovir and valacyclovir) is common pre-, during and, post-transplant. The question then becomes how effective these drugs are to spare us from shingles and/or PHN. Seventeen studies provide answers.

• Your cumulative risk of ending up with shingles and/or PHN increases with the amount of time you have spent in treatment of your myeloma (or other cancer that involved a STC). In other words : the longer you have lived with myeloma, the higher your risk of ending up with shingles.
• ‘The duration of antiviral prophylaxis appears to modify risk of HZ; HCT patients who received short-term prophylaxis had the highest cumulative incidence of zoster at a given follow-up time.’ Or, the sooner you stop your anti-viral therapy, the higher you increase the risk to come down with a case of shingles in the future.
• “The effect of long-term prophylaxis against HZ persists at one year after prophylaxis is discontinued”. In other words, even after you stop taking your antiviral drugs, you will still have some protection for a period of a year.
• ‘… by 5 years post-transplant, the HZ risk of patients who received 12 months of prophylaxis was similar to that of patients who received no’ [emphasis added]

Following our diagnosis with myeloma, all of us ended up with a fistful of prescriptions of medications we weren’t familiar with. I am going to assume that just about all of us don’t particularly enjoy popping pills. In the case of the antiviral drugs used in the prophylaxis of shingles/PHN, this research article makes it quite clear that stopping antiviral therapy is NOT a good idea.  When you decide to do so, you must do so with wide open eyes that your chance of ending up with shingles, and later on with PHN, increases with the length of time after you stopped taking those two pills per day.

You can raise the question then, ‘How about the shingles vaccines that are currently on the market ? Are they an option to avoid shingles in the future?’ There are two FDA-approved shingles vaccines : Zostavax (approved in 2006) and Shingrix (approved in 2017). Zostavax is a ‘live vaccine’ and is therefore an absolute no-no for transplant patients. And that leaves us with Shingrix, which is an ‘inactivated’ vaccine. The question can then be rephrased as, ‘Does the Shingrix vaccine offer a good alternative for the prevention of shingles in patients who have received a stem cell transplant ?’. Unfortunately, there is only one large scale study that offers some answer. ‘Bastidas and colleagues … randomized 1,846 adults who had recently undergone HSCT and found that a 2-dose course of a recombinant zoster vaccine reduced the incidence of herpes zoster over a median follow-up of 21 months.’ Eyeballing a chart embedded into this last referenced article indicates that the incidence of shingles is reduced by about 2/3, compared to no prophylaxis at all, and that this effect is most pronounced in the earlier period post dosing with Shingrix. At the 42-month point, 3 ½ years, the incidence rate of patients vaccinated with Shingrix dropped to about ½ of those without any prophylaxis. Shingrix offers some protection against shingles but is not perfect. The authors of the original article quoted above conclude:

‘Although HZ is thought to be more severe in immunocompromised patients, and early data suggest the benefits of vaccination in some patient populations [see the Bastidas article quoted above], high quality data on complications and severity are required to evaluate the cost-effectiveness of vaccination for these populations.  This additional information will be critical to inform policy decisions for HZ vaccines in immunocompromised populations in the US.’

In other words, the authors hedge their bet a bit with the above quotation as to whether Shingrix vaccination should become the ‘standard of care’ for the prevention of shingles or PHN as, currently, not enough is understood yet as to what its true long-term efficacy is the population of immunocompromised patients (including us, SCT patients).

The study that would provide more guidance to us, stem cell transplant patients, would be to compare oral medication prophylaxis (both short- and long-term courses of treatment) against the two-dose schedule of injected Shingrix vaccine and monitor the enrolled patients over a prolonged period. That would give us the clarity of what would truly offer us the best protection against both shingles and post herpetic pain in the future. By now, you are, quite likely, confused about what to opt for. I suggest that you discuss your options with your myeloma specialist who will most likely refer you to an infectious disease specialist who will be on staff in any of the myeloma ‘centers of excellence’.