In the past 8 years, however, thalidomide, bortezomib, and very recently lenalidomide, when combined with conventional doses of alkylators and corticosteroids, have produced marked improvements in progression-free survival (PFS) and overall survival (OS) in elderly patients.
Full Answer
What is the best treatment for multiple myeloma in the elderly?
For more than 40 years, melphalan plus prednisone (MP) was the standard of care for patients with MM. However, in the last 20 years the proteasome inhibition has been one of the most relevant steps to improve the survival of elderly patients with newly diagnosed MM (NDMM).
Is autologous stem cell transplantation safe in elderly multiple myeloma?
· Corticosteroids, novel agents, conventional cytotoxic agents, and high-dose chemotherapy with autotransplantation (modalities used in younger patients) are also used in older patients, although the elderly undergo transplantation less frequently.
What is the prognosis of multiple myeloma over 65 years old?
· Novel agents have been added to the treatment of elderly patients in three ways: the addition of one novel agent to the MP combination, the addition of one novel agent to dexamethasone, and the use of a novel agent as maintenance therapy after induction treatment. TABLE 2 . Randomized Studies Comparing MP and MPT Regimens: Results. MP-Based ...
Is there a role for ahsct in elderly myeloma?
· Options for treatment of elderly patients abound. Current favorites, depending on region and drug availability, include lenalidomide/dexamethasone, 7 VRd, 99 VMP, 6 and ASCT. Triplet therapy including a proteasome inhibitor and an immune-modulating drug and ASCT is associated with the deepest responses and, in most instances, with better PFS and OS.
How is multiple myeloma treated in the elderly?
Corticosteroids, novel agents, conventional cytotoxic agents, and high-dose chemotherapy with autotransplantation (modalities used in younger patients) are also used in older patients, although the elderly undergo transplantation less frequently.
What is the latest treatment for myeloma?
The latest approval is for the combination of daratumumab plus hyaluronidase-fijh (Darzalex Faspro) plus carfilzomib (Kyprolis) and the steroid dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who received one to three prior treatments.
How is relapsed myeloma treated?
The standard treatment of relapsed multiple myeloma has been either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for 2 reasons.
What are the symptoms of end stage multiple myeloma?
But when you have late-stage multiple myeloma, your symptoms may show up as:Being sick to your stomach.Bone pain in your back or ribs.Bruising or bleeding easily.Feeling very tired.Fevers.Frequent infections that are hard to treat.Losing a lot of weight.Not feeling like eating.More items...•
What is the best maintenance drug for multiple myeloma?
Maintenance treatments containing the immunomodulatory therapy Revlimid (lenalidomide) are the best option for patients with multiple myeloma, according to a recent meta-analysis. The study, “Maintenance Treatment and Survival in Patients With Myeloma,” was published in the journal JAMA Oncology.
What is the most successful treatment for multiple myeloma?
Chemotherapy. Chemotherapy uses drugs to kill cancer cells. The drugs kill fast-growing cells, including myeloma cells.
What is second line treatment for multiple myeloma?
Second-line therapy daratumumab, bortezomib and dexamethasone. lenalidomide and dexamethasone. carfilzomib and dexamethasone. bortezomib and dexamethasone.
What happens when multiple myeloma relapses?
If your doctor tells you that you're having a relapse, it means your multiple myeloma came back after your treatment left you cancer-free for a while. If this happens to you, keep in mind that there are still treatments that can help. It's a matter of finding the drug or combination of drugs that works for you.
How is multiple myeloma 2021 treated?
Monoclonal antibodies (updated 12/2021). Daratumumab may be given to treat newly diagnosed multiple myeloma. A drug combination of daratumumab and hyaluronidase-fihj (Darzalex Faspro) with or without pomalidomide (Pomalyst) and dexamethasone (multiple brand names) may also be used to treat multiple myeloma.
What foods help multiple myeloma?
That can cause a shortage of red blood cells, called anemia. If this happens, you may need to eat more iron-rich foods, like: Lean meats....Fiber.Fruits like apples and pears.Dried fruits like figs and prunes.Whole grains.Oatmeal and other cereals.Nuts and beans.Vegetables like broccoli, carrots, celery, and artichokes.
What happens if you stop treatment for multiple myeloma?
But when treatment stops working, myeloma cells start growing again. It's called a relapse. Relapse is common for people with multiple myeloma. In fact, this cancer is known as a “remitting and relapsing” disease.
What is the life expectancy for myeloma patients?
5-year relative survival rates for myelomaSEER stage5-year relative survival rateLocalized (solitary plasmacytoma)78%RegionalNot applicableDistant (multiple myeloma)55%All SEER stages combined56%Mar 2, 2022
What is the best treatment for symptomatic myeloma?
The basic choice is between active therapy (most patients) and palliation (selected patients). Active therapy choices include stem-cell sparing induction therapy with a view to possible AHSCT at some point, melphalan-prednisone with one of the novel agents, or other multidrug combinations. Interestingly, the Ld combination (lenalidomide and weekly dexamethasone) is commonly used even in patients who are ineligible for HSCT because of its excellent tolerance. 19
Why is myeloma delayed in older people?
The diagnosis of myeloma may be delayed in older persons because early nonspecific symptoms, such as fatigue, bone pain, and susceptibility to infections, may be attributed to other causes.
What is the treatment for AHSCT?
The general scheme of disease-specific therapy is illustrated in Figure 1. Patients eligible for AHSCT should receive induction therapy that excludes melphalan to avoid irreversible stem cell damage. This usually composes 2 or 3 drugs: a novel agent (thalidomide, lenalidomide, or bortezomib) with corticosteroids with or without a cytotoxic agent, or 2 novel agents with corticosteroids. Response rates and EFS are higher with 3-drug combinations compared with 2 drugs in younger patients. Those who are clearly ineligible for AHSCT usually receive induction therapy that is based on one of the novel agents: combined with melphalan-prednisone (MP) or with corticosteroids.
Why is individualization important in myeloma?
Individualization of management and adequate supportive therapy are important to obtain the best response while minimizing adverse effects.
Why is it important to maintain hemoglobin levels before serum protein levels rise?
Maintaining adequate hemoglobin and starting therapy before serum protein rises to levels that can increase whole blood viscosity significantly are important in patients with cardiovascular disease to minimize the risk of ischemic episodes and heart failure.
What is the goal of complete remission?
If significant toxicity is seen, obtaining good disease control while maintaining quality of life is reasonable. Prolongation of remission and survival are additional goals. Symptom control is achieved through effective disease-specific and supportive therapy.
Is corticosteroids good for palliation?
There is a small subgroup of much older persons (≥ 80 years; with other serious comorbidities) in whom palliative therapy is a reasonable option. The use of corticosteroids can result in effective palliation as well as some cytoreduction.
What is the best treatment for multiple myeloma?
Novel agents (thalidomide, lenalidomide, bortezomib) are dramatically changing frontline therapy of MM. Randomized studies have shown the superiority of adding one novel agent to MP, either thalidomide (MPT) or bortezomib (MPV). The combination of lenalidomide with low doses of dexamethasone is another attractive alternative. Recent results show that maintenance therapy with low-dose lenalidomide may prolong progression-free survival. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial.
What is maintenance therapy?
Maintenance Therapy. The goal of maintenance therapy is to increase the duration of remission by controlling the malignant clone. In the past, interferon produced a moderate increase in PFS, [21] but because of toxicity, long-term treatment could not be justified.
How many cycles of Bortezomib combined with doxorubicin and dexamet
Four cycles of bortezomib combined with doxorubicin and dexamethasone (PAD regimen) were administered in 102 patients aged 65 to 75 years. The rate of CR plus VGPR was 58%. Because the induction treatment was effective and well tolerated, 90% of patients received the first ASCT and 83% received the second. After ASCT, patients received lenalidomide consolidation/maintenance therapy, and the final rate of CR plus VGPR increased to 78%, with very encouraging 2-year PFS and OS rates of 69% and 86%, respectively.
How long does Melphalan last?
One might speculate that higher doses of melphalan (0.25 mg/kg/d for 4 days every 6 weeks) and thalidomide (200 mg/d for 1 week, and up to 400 mg/d) and inclusion of older and more frail patients were the reason that a better response rate did not translate into a longer PFS in the MPT arm.
What is the MM stage?
MM is a late stage in the evolution of monoclonal gammopathies and is always preceded by a phase of monoclonal gammopathy of unknown significance (MGUS)-although this phase is not always recognized. An intermediate stage is smoldering (or asymptomatic) myeloma (SMM).
Which is better, immid or bortezomib?
Most of these criteria are patient-related. Bortezomib-based regimens are preferred in patients with renal failure or a previous episode of deep vein thrombosis. IMiD-based regimens are preferred when oral administration is more suitable. Lenalidomide-based regimens are preferred in patients with concomitant peripheral neuropathy, since both thalidomide and bortezomib are potentially neurotoxic.
Is MPT a standard of care?
As a consequence of these studies, the regimen MPT is now considered a new standard of care and it has been approved by the European Medicines Agency (EMEA) for the treatment of patients older than 65 years with newly diagnosed MM. However, safety may be a concern, especially in very old or frail patients. For example, in the Nordic trial, the median patient age was 78 years, and the proportion of patients with an Eastern Cooperative Oncology Group (ECOG) performance status higher than 2 was 30%. [12] This high incidence of more frail patients resulted in a high rate of toxic death (23 deaths in the first 6 months in patients over 75 years of age in the MPT arm versus a rate of 12 deaths during the first 6 months in the MP arm) and lower compliance with treatment (59 treatment discontinuations in the MPT arm versus 18 in the MP arm). As a consequence, PFS was not improved in the MPT arm. One might speculate that higher doses of melphalan (0.25 mg/kg/d for 4 days every 6 weeks) and thalidomide (200 mg/d for 1 week, and up to 400 mg/d) and inclusion of older and more frail patients were the reason that a better response rate did not translate into a longer PFS in the MPT arm. [12]
What percentage of patients with multiple myeloma are diagnosed at age 75?
Multiple myeloma is a plasma cell malignancy that occurs among older adults and accounts for 15% of all hematologic malignancies in the United States. Thirty-five percent of patients are diagnosed at age 75 or older.
What is the standard of care for MM?
Treatment intensity and clinical decision making for patients with MM relies on chronologic age, comorbidities, and performance status. 10 - 12 These factors oversimplify the complexity of caring for older adults and are often unable to identify the heterogeneity associated with aging. Treatment stratification for MM has been age based, in which clinical trials of transplant versus nontransplant strategies are conducted for those younger or older than age 65, respectively. ASCT is considered the standard of care; however, transplantation is less frequently performed for adults age 65–74 and rarely in those age 75 or older. 13 Balancing the toxicities of transplantation with survival advantages is challenging for the older adult. ASCT recipients report variable improvement in health-related quality of life (HRQoL) 14 and substantial short- and long-term morbidity, 15, 16 and they can develop nonmalignant late effects that negatively affect overall health and functional status. 17 Older adults with MM are vulnerable to adverse events associated with multidrug combinations, which can lead to dose reductions or cessation of therapy and are associated with poorer outcomes. 18 Elderly age and frailty are not synonymous. Identifying factors that contribute to poor physiologic reserve and make patients vulnerable to treatment toxicity are under active investigation in MM. Frailty is a clinical syndrome, distinct from disability and comorbidities, in which cumulative factors of unintentional weight loss, self-report of exhaustion, weakness, slow walking speed, and/or low physical activity confer worse survival when present. 19 Some MM studies suggest frailty as patients older than age 75 or younger patients with abnormal organ function 20; others have suggested treatment strategies with dose-level reductions based on risk factors of age 75 or older, help with activities of daily living (ADLs), and/or end organ dysfunction. 21 Understanding risk stratification and physiologic age is critical to reducing disparities when treating older adults with MM.
How much is the mortality rate for Melphalan?
However, high-dose melphalan with autologous ASCT is still associated with notable morbidity and a mortality rate that can be as high as 10% at 1 year for older and debilitated patients with a poor performance status.
What is the comorbidity index for hematopoietic cell transplantation?
The hematopoietic cell transplantation comorbidity index (HCT-CI) was developed by Dr. Mohamed Sorror to predict survival and NRM in the allogeneic setting. However, this index is also shown to also predict NRM risk after autografts. Saad et al 84 studied 1,156 autograft recipients after they received high-dose melphalan, using data reported to the Center for International Blood and Marrow Transplant Research. Participants were stratified into three risk groups: HCT-CI of 0 (42%) versus HCT-CI of 1–2 (32%) versus HCT-CI of more than 2 (26%). One-year NRM was low at 2% and did not correlate with HCT-CI score. On multivariate analysis, OS was inferior in groups with an HCT-CI of 1–2 or more than 2. 21 For younger patients, the Karnofsky performance status predicts for higher NRM and worse HCT outcomes. 21 Thus, our current recommendation is not to pursue high-dose melphalan for older patients with poor performance status (Karnofsky performance status of 80 or less).
What are the complications of Melphalan?
Of note, atrial arrhythmias and supraventricular tachycardias are more common with high-dose melphalan than other conditioning regimens, and retrospective analysis has shown that increasing age is a predictor of this complication. 79
Is ASCT performed more frequently for older patients?
ASCT is being performed more frequently for patients older than age 60, with improvements in NRM and overall outcomes. Table 2 summarizes the largest registry series published to date. These reports, together with multiple single-center reports, demonstrate that autologous ASCT is feasible for older patients with MM, that NRM is routinely less than 5%, and that results are comparable or only slightly inferior to those of younger patients. 77, 78
Is MM a good indication for ASCT?
MM is the most common indication for ASCT in North America today. Although randomized trials have shown the benefit of high-dose melphalan for patients younger than age 65, this procedure is now routinely performed for patients up to age 80, 69, 70 o wing to recent advances in supportive care and the use of filgrastim-mobilized peripheral blood. However, fewer than 20% of all patients age 65 or older are undergoing the procedure. 13
What is a MM patient?
Multiple myeloma (MM) is a clonal disorder of malignant plasma cells that comprises approximately 10% of hematologic malignancies. The median age at diagnosis is 66 years, making it predominantly a disease of the elderly. Multiple myeloma accounts for approximately 1%-2% of all cancers and slightly more than 17% of hematologic malignancies in the United States [1]. The annual incidence of MM in the United States is approximately four to five per 100,000. The incidence increases with age and combined with the worldwide increase in the elderly population, there is an anticipated 77% increase in the number of patients older than 65 years diagnosed with MM each year by 2030 [2-4]. Development of newer therapeutic agents and improving supportive care over the last two decades has significantly improved the outcome of MM in younger patients [5-7]. However, most studies suggest that improvements are marginal in elderly patients (defined as age 75 years and older) [2, 6]. This may be explained by the higher incidence of more severe disease in the older patients, but it is mainly due to patient characteristics (e.g. performance status, comorbidities) and organ dysfunction associated with aging [5-7].
Is bortezomib a proteasome inhibitor?
Bortezomib, the first-in-class proteasome inhibitor, is another important option for frontline therapy in elderly patients with MM. A large phase III randomized trial called Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA) compared MP and bortezomib plus MP (MPV) in a series of 682 newly diagnosed MM patients [26]. MPV was significantly superior to MP in ORR (71% vs. 35%), CR rates (30% vs. 4%). An updated analysis of the data with a median follow-up of five years demonstrated significant OS benefit with MPV vs. MP, with 13.3 month increase in the median OS (56.4 months vs. 43.1 months) [27]. Based on these data, MPV is recognized as standard of care regimen for use in elderly patients. However, safety was a concern in elderly patients; in the MPV arm, the incidence of grade 3 or grade 4 peripheral neuropathy was 14%, and 30% of patients had to discontinue treatment or at least discontinue bortezomib because of treatment-related adverse events [26].
Is lenalidomide more potent than thalidomide?
Lenalidomide, thalidomide’s next generation analog, is more potent and less toxic than thalidomide. A randomized phase III trial compared MP versus a combination of melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance (MPR or MPR-R) [21]. Preliminary results of the study showed MPR-R was significantly superior to MP with higher response rates (77% vs. 50%) and greater CR rates (18% vs. 5%), superior to MPR in terms of PFS [2, 21-23]. The toxicity profile is less when compared with MPT and the common adverse events observed were neutropenia, thrombocytopenia, and infections.
You lectured on elderly patients with multiple myeloma. What is important to know about this subset?
Rosko, an assistant professor in the Division of Internal Medicine, The Ohio State University Comprehensive Cancer Center, spoke on treatment approaches for elderly patients with multiple myeloma at the 2017 OncLive® State of the Science Summit TM on Hematologic Malignancies.
What supportive care measures are being used?
When it comes to relapsed myeloma, that is one of the areas that is ever changing and harder to talk about in a short amount of time. However, one of the agents that has significantly changed the landscape of multiple myeloma is the use of Darzalex (daratumumab) in the relapsed setting.
Are there ongoing trials exploring therapies for elderly patients with myeloma?
Patients with multiple myeloma have among the poorest quality of life especially when it comes to hematologic malignancies. Being able to better optimize the factors related to aging is quite important.
Regarding the clinical trials that were halted exploring checkpoint inhibition in multiple myeloma, are such serious adverse events experienced in older patients?
Also, we are looking at all-oral regimens in the frontline setting. It is also very important so patients don’t have to be in clinic as much in terms of travel burden and financial burden, too. Melphalan is tricky because it’s been around [for a while] and has significant response rates that are quite impressive.
How to reduce risk of multiple myeloma?
If you have (or have had) multiple myeloma, you probably want to know if there are things you can do that might lower your risk of the cancer growing or coming back, such as exercising, eating a certain type of diet, or taking nutritional supplements. Adopting healthy behaviors such as not smoking , eating well , getting regular physical activity, ...
How long does cancer treatment last?
Almost any cancer treatment can have side effects. Some last for a few weeks to several months, but others can be permanent. Don’t hesitate to tell your cancer care team about any symptoms or side effects that bother you so they can help you manage them.
How to plan for cancer survivorship?
Talk with your doctor about developing a survivorship care plan for you. This plan might include: 1 A suggested schedule for follow-up exams and tests 2 A schedule for other tests you might need in the future, such as early detection (screening) tests for other types of cancer, or tests to look for long-term health effects from your cancer or its treatment 3 A list of possible late- or long-term side effects from your treatment, including what to watch for and when you should contact your doctor 4 Diet and physical activity suggestions 5 Reminders to keep your appointments with your primary care provider (PCP), who will monitor your general health care
What to do after cancer treatment?
During and after treatment, it’s very important to go to all follow-up appointments. During these visits, your doctors will ask about symptoms, examine you, and order blood tests or imaging studies such as CT scans or x-rays. Follow-up is needed to see if the cancer has come back, if more treatment is needed, and to check for any side effects. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have.
Do supplements help with cancer?
About dietary supplements. So far, no dietary supplements (including vitamins, minerals, and herbal products) have been shown to clearly help lower the risk of cancer progressing or coming back. This doesn’t mean that no supplements will help, but it’s important to know that none have been proven to do so.
Does cancer go away?
For other people, the cancer might never go away completely. Some people may get regular treatment with chemotherapy and other drugs, radiation therapy, or other treatments to try and help keep the cancer in check. Learning to live with cancer that does not go away can be difficult and very stressful. Life after multiple myeloma means returning ...
Does eating well help with myeloma?
Adopting healthy behaviors such as not smoking , eating well , getting regular physical activity, and staying at a healthy weight might help, but no one knows for sure. However, we do know that these types of changes can have positive effects on your health that can extend beyond your risk of myeloma or other cancers.