CHALLENGES AND LESSONS LEARNED IN THE MANAGEMENT OF MULTIPLE MYELOMA IN THE SETTING OF COVID-19

May 2021 Covid-19 Willem van Altena

Interview with prof. Michel Delforge (UZ Leuven) on the treatment of Multiple Myeloma in the setting of COVID-19

Haematologic patients who contract a COVID-19 infection have an overall mortality risk of 34%, according to an international study among patients from 40 countries.1 The mortality risk of hospitalized haematologic patients with COVID-19 was 39%. Professor dr. Michel Delforge, haematologist from UZ Leuven and specialist on the treatment of Multiple Myeloma discusses the challenges of MM care during the COVID-pandemic.

Patients with Multiple Myeloma (MM) who contract COVID-19 seem to be at increased risk of a more severe COVID19-infection, associated complications and a higher mortality rate. Can you explain the reasons and possible mechanisms behind this? How can we lower these risks?

“There  are indeed several reasons for this and not all of them are specific to myeloma. An obvious reason is that MM generally affects elderly patients, and as we all know, elderly persons have a higher risk for mortality or severe complications of a COVID-19 infection. A more specific reason is that MM is a systemic cancer that affects many parts of the immune system, unlike a localized cancer such as breast cancer. This is an intrinsic reason why MM patients can have more serious infections, and this includes COVID-19. Furthermore, MM is a chronic disease with remissions and relapses, so many patients have received multiple lines of treatment. Because of that they also have an even more depleted immune system, which unfortunately is associated with more severe infections. A final reason for the increased risk for MM patients of a severe COVID-infection can be found in a decreased renal function, which affects 25 to 33% percent of MM patients.”

“As for treatment, there have been studies addressing this topic even though the data do not give a 100% conclusive answer. One of these studies was published in Blood last year, by dr. Chari et al.,2 who studied the outcome of COVID-19 among 650 MM patients from different countries. Mortality was 1 out of 3 patients, and multivariate analysis found that age, high-risk MM, renal disease and suboptimal MM control were independent predictors of adverse outcome with COVID-19 infection.”

“Lowering risk factors for people with MM contracting a severe COVID-19 infection is not always an option, because certain factors such as age or stage of the disease cannot be controlled. But taking preventive measures to avoid getting infected with COVID-19 is of course possible.”

Are adaptations in standard treatment regimens necessary due to COVID-19? For instance, due to the pandemic, frequent hospital visits should be avoided. However, standard of care in MM is daratumumab, which requires relatively many hospital visits due to its intravenous administration. Could oral regimens give advantages in this setting? And have other measures been put into place for the treatment of MM patients in Belgium?

“In hospitals, several efforts have been made to try to reduce the risk for COVID-19 infections and many of those are based on common sense and on general rules of preventive medicine. But there can be significant differences from one country to another, and within the country from one centre to another. Considering the fact that a hospital is a place with an increased risk of infection, one should try to make every effort avoiding that patients have to come too often to the hospital. In a very large hospital like UZ Leuven we were able to completely separate flows of vulnerable patients and possibly COVID-infected patients, but many smaller hospitals were less able to do so.”

“This is also the reason why drugs with an oral or subcutaneous route of administration were often preferred since these require fewer hospital visits. Especially now that most healthcare workers have been vaccinated, treatments at home have really become an even more viable option during the last month or so. In addition, there also have  been discussions regarding increasing the interval between drug administrations in certain treatment regimens, of course always in a safe way without putting the outcome of the patients at risk in terms of disease control. Many of these approaches have been tried, especially during the first critical phase of the pandemic when many hospitals were overwhelmed, but these approaches were not evidence-based. Perhaps, when a patient is undergoing maintenance treatment there is some dosing flexibility possible, but when a patient has rapidly progressive disease this is not the case. Personally, I would be careful to say we need to switch all patients to oral regimens. We need to reduce the frequency of hospital visits, but without losing the quality of care.”

Regarding delay of treatment: should a treatment be interrupted in MM patients with symptomatic COVID-19 disease?

“I would not be in favour of interrupting a treatment for too long because there is no clinical or scientific evidence to back this up. In some cases this is an option, for instance when it concerns medication that is administered for supportive care that does not really impact the prognosis, like bisphosphonates, which increase bone health in patients. But when an interruption concerns active anti-myeloma treatments I am much more cautious, because there is not enough scientific data to support the idea that postponing treatment can be done safely. A year ago, when we were in a crisis situation sometimes, choices to postpone treatments had to be made. I do think that, when this crisis is over, there will be lessons learned, for instance, regarding limiting the need for hospital visits for patients.”

Should autologous or allogeneic stem cell transplantations be postponed for MM patients with COVID-19? And why should especially allogeneic transplantations be postponed compared to autologous transplantations?

“The initial guidelines concerning autologous or allogeneic stem cell transplants for MM patients recommended that these could safely be postponed to a later date as long as other treatments continued. However, in Leuven we did not follow this recommendation because UZ Leuven is a very large hospital where we could safely perform these procedures in a highly protected area with rigorous safety measures. Everybody who entered the hospital for an overnight stay had to undergo a meticulous screening for COVID a maximum of 24 hours prior. So we felt like we could safely continue with autologous stem cell transplants. I fully understand that some centers did have to postpone stem cell transplants. Allogeneic transplants were another matter since these involve a stem cell donor, thus increasing risk factors, but we do not perform many allogeneic stem cell transplants anymore, anyway.”

Should there be a case-by-case assessment when it comes to the treatment of MM patients with a COVID-19 infection, and can you highlight which criteria come into play?

“Perhaps contradictory: MM patients with highly active disease tend to also have the highest mortality risk if they would get a COVID-19 infection. In this case I think we should make every effort to continue treatment, while being very meticulous in the prevention of COVID-19 infection. If such  patients would get COVID-19, they would be at high risk of mortality, but on the other hand, we do not want to risk contributing to a refractory myeloma. We therefore have to adopt a case-by-case approach. Perhaps for younger patients we would adopt a different approach than for frail and elderly patients.

Can you elaborate on the current views regarding COVID-vaccination for MM patients? Should they be vaccinated and is the vaccine as effective for them as it is for others? Is there already concrete data available that indicates how well the vaccines protect MM patients?

 “Every day we get many questions from patients regarding COVID-vaccination and whether it is advisable for them to be vaccinated and how well it will protect them. I believe that MM patients should always be vaccinated. However, the performance of the COVID-19 mRNA vaccines in haematological malignancy patients is unknown, as these patients were excluded from COVID-19 vaccine clinical trials.3.4 We learn to know more about vaccination efficiency in myeloma patients after the first injection of an mRNA vaccine.5 From the very preliminary results we learn that patients with myeloma have a lower seropositivity rate compared to healthy controls, particularly in patients with active disease and those receiving treatment. The good news however is that there seems to be little difference between types of vaccine. It is clear that the corona virus will remain among us for the foreseeable future and we need to unravel how to avoid people from falling severely ill, especially those with depleted immune systems such as MM patients.”

What are the most important lessons learned from this past pandemic year with respect to haematologic clinical practice and MM treatments?

“On the one hand we have seen the fragility of our healthcare system, and at the same time also the strength of it in countries like Belgium and the Netherlands. Our healthcare system is flexible, adaptable and able to cope with a crisis like this. Yet at the same time we need to remain critical of how we do things. Sometimes we do things out of a sense of tradition and we need to challenge that. We also need to seriously think about how we can limit the number of hospital visits. What can we do in an outpatient-setting when it comes to myeloma management? This might well be the most important lesson for the future. We need to further develop safe quality home care, such as subcutaneous administration. After all, for patients it is much more comfortable to receive care in their own home instead of having to go to the hospital.”

To conclude, how do you see the future after the pandemic concerning the care for MM patients and for Belgian healthcare as a whole?

“We need to be prepared for a next crisis because a new virus will appear someday. And when it comes to lessons learned from this crisis, I think it will take a while before we understand the full impact COVID-19 has had, also financially. Multiple Myeloma is an expensive illness to treat, as is cancer. We live in a country with a robust and healthy healthcare system but we can only spend every euro just once. And if I could add one last lesson we need to take home from the COVID-19 crisis is that we Belgian haematologists really need to collaborate as much as we can and build a better understanding. Working together during difficult times is the only way forward.”

‘We need to reduce the frequency of hospital visits, but without losing quality of care’

References

  1. Vijenthira A, Gong IY, Fox TA, et al. Epidemiological data of haematologic disease and COVID-19, Outcomes of patients with haematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients. Blood. 2020 Dec 17;136(25):2881-2892. doi: 10.1182/blood.2020008824. PMID: 33113551; PMCID: PMC7746126.
  2. Chari A, Samur MK, Martinez-Lopez J, et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood. 2020 Dec 24;136(26):3033-3040. doi: 10.1182/blood.2020008150. PMID: 33367546; PMCID: PMC7759145.
  3. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS172 CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-416.
  4. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA174 Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615.
  5. Bird S, Panopoulou A, Shea RL, et al. Response to first vaccination against SARS-CoV-2 in patients with multiple myeloma. Lancet Haematol. 2021 Apr 19:S2352-3026(21)00110-1. doi: 10.1016/S2352-3026(21)00110-1. Epub ahead of print.

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