CHRONIC-RHINOSINUSITIS-WITH-NASAL-POLYPS-CRSWNP

RESPIRATORY

Hear from an expert on how can you limit the effects of systemic steroid use for Patients with CRS with Nasal Polyps?

The superiority of Biologics over OCS for disease modifying potential which explains the superiority over OCS as anti-inflammatory option for our patients with CRSwNP, when we prescribe the Biologicals, we prescribe them long term for chronic disease where we do believe that we do not only aim to reduce inflammation but also to have some disease modifying effects.

Expert opinions: Would you consider a biologic for a CRSwnp patient who has had Sinus surgery?

It's not just about surgical skills or extent of surgery, it's also about the environment and what drives the inflammation in our patients.

Beginning early in multiple sclerosis (MS), smoldering neuroinflammation can be largely unseen and lead to disability accumulation.1,3 But there is hope.

<h3>ONCE SPARKED SMOLDERING NEUROINFLAMMATION IS DESTRUCTIVE1,2</h3>

black

MULTIPLE-SCLEROSIS

NEUROLOGY

Smoldering Neuroinflammation

Tolebrutinib Direct Effects on Myeloid Cells in PwMS

Inside MS: Explore how BTK drives immune cell activation and CNS damage

Discover the science behind Tolebrutinib: a BTK inhibitor designed to slow MS disability progression by modulating adaptive and innate immunity

The Role of the CNS and Periphery in MS and Disease Accumulation

Renal impairment is a common complication in patients with multiple myeloma

Patients with renal impairment are o en excluded from or underrepresented in clinical trials1

...and it forms a core part of the&nbsp;CRAB criteria&nbsp;used to diagnose multiple myeloma2,3

Renal impairment adversely affects survival

The median survival of patients with renal impairment is approximately half that of patients without renal impairment4

There are multiple contributors to renal impairment2

Depth of renal impairment at diagnosis is predictive of poor prognosis6
eGFR (mL/min/1.73m²)

References

MULTIPLE-MYELOMA

HEMATOLOGY

Multiple Myeloma: Renal Impairment

Patients with multiple myeloma who achieve minimal residual disease (MRD) negativity have been shown to have better outcomes compared with MRD positive patients1

Achieving deeper responses can improve outcomes2

Sustained MRD– = MRD– for 1 year

MRD is the low level of malignant cells that persist even after a complete response with myeloma treatment1

<h2>The methods used for determining MRD negativity include:</h2>

<h2>Achieving MRD negativity is associated with better outcomes such as longer PFS and OS compared with patients who are MRD positive6,7</h2>

Meta-analysis of 43 studies involving 8,114 patients:

Meta-analysis of 22 studies involving 4,462 patients:

<h2>MRD negativity is being considered as a regulatory surrogate endpoint for PFS8,9</h2>

Abbreviations

Multiple Myeloma: Minimal Residual Disease

Learning aRMMs

<h2>Type 2 Inflammation in Chronic Rhinosinusitis with Nasal Polypolis (CRSwNP)</h2>

About Type 2 Inflammation – Nasal Polyps

<h2>CRSwNP is a Chronic Type 2 Inflammatory disease with high symptom burden and substantial unmet need</h2>
<h3>CRSwNP patients experience high symptom burden and have a reduced health-related QoL²</h3>
Nasal Symptoms
<ul>
 <li>Congestion</li>
 <li>Sneezing</li>
 <li>Loss of smell/taste</li>
 <li>Runny nose</li>
 <li>Nasal discharge</li>
</ul>
Ear and Facial Symptoms
<ul>
 <li>Facial pain</li>
 <li>Facial pressure</li>
 <li>Ear pain</li>
 <li>Ear pressure</li>
 <li>Dizziness</li>
</ul>
Health-Related QoL Impact
<ul>
 <li>Difficulty falling/staying asleep</li>
 <li>Fatigue</li>
 <li>Waking up tired</li>
 <li>Reduced concentration</li>
 <li>Reduced productivity</li>
</ul>
Psychological Symptoms
<ul>
 <li>Frustration, restlessness, irritability</li>
 <li>Sadness</li>
 <li>Embarrassment</li>
</ul>

Reference

<ul>
</ul>
<h2>CRSwNP patients often have coexisting Type 2 Inflammatory disease1,2</h2>
<ul>
 <li>50% Asthma&nbsp; &nbsp;</li>
 <li>75% Allergic&nbsp;Rhinitis</li>
 <li>10-20% NSAID-ERD</li>
</ul>

<h2>Conventional therapy, including steroid bursts and surgery, does not always provide long-term relief</h2>
<ul>
 <li>Treatment guidelines recommend cautious use of systemic steroids ⁵⁻⁹</li>
 <li>Systemic steroids&nbsp;are not recommended as chronic therapy because of the risk of serious adverse effects with long-term use</li>
 <li>Difficult-to-treat patients are often refractory to medical and surgical management ¹⁰ 35%&nbsp;of patients experience polyp recurrence within 6 months of surgery</li>
</ul>

80%&nbsp;of patients with CRSwNP have type 2 inflammation, which contributed to symptoms and polyp formation7,a
ᵃIn Western countries

<h2>IL-4 and IL-13 are Key and Central Drivers of Type 2 Inflammation</h2>
<h3>IL-4 and IL-13 are central type 2 cytokines that have shared and distinct roles in the pathophysiology of CRSwNP1,2</h3>

Abbreviation

<h2>Multiple Myeloma: Cytogenetic abnormalities</h2>
The presence of high-risk cytogenetic features has been well documented as a negative prognostic factor and these patients typically have poorer outcomes compared with standard risk patients1,2

Patients with high-risk cytogenetics are not always captured in clinical trials or real-world studies resulting in subgroup analyses on a relatively small sample size3–5

Consequently, there is a paucity of data for the targeted treatment of patients with high-risk cytogenetics and randomized trials are needed in these populations5

Genomic instability and heterogeneity are hallmarks of multiple myeloma1,6

<h3>Multiple myeloma: cytogenetic abnormalities1,6,12</h3>

Trisomies&nbsp;~50% of cases

Duplications of entire chromosomes 
 Typically involves chromosomes 3, 5, 7, 9, 11, 15, 19 or 21

Translocations&nbsp;40–70% of cases

Translocations involving the immunoglobulin heavy-chain gene on chromosome 14

Deletions&nbsp;7–50% of cases

Loss of chromosomes or sections, resulting in haploinsu ciency 
 Typically involves chromosomes 1, 6, 8, 13, 11, 14, 16 or 17

Gains&nbsp;~40% of cases 
 &nbsp;

Duplication of chromosomes or sections Frequently a ects chromosome 1q

<h2>Cytogenetic analysis of bone marrow samples by fluorescence in situ hybridization (FISH) is recommended at diagnosis for risk stratification1,13,14</h2>
The IMWG use the following cytogenetic abnormalities identified by FISH to define multiple myeloma with poor prognosis:1

t(14;20)&nbsp;1&nbsp;%&nbsp;of MM cases

t(14;16) &nbsp;4% of MM cases*

del(17/17p)&nbsp;7%&nbsp;of MM cases*

t(4;14)&nbsp;15%&nbsp;of MM cases*

gain(1q)&nbsp;40%&nbsp;of MM cases

*Included in the Revised International Staging System for multiple myeloma as high-risk15

<h2>Gain of chromosome 1q is commonly found in patients with MM and frequency increases with disease progression16</h2>
Gain 1q is a poor prognostic factor with a negative impact on survival outcomes particularly when there are more than&nbsp;4 copies&nbsp;present or if it is associated with other high-risk cytogenetic abnormalities

<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>There is inconsistency in clinical trials in the cut-o used to define the existence of a high-risk abnormality ranging from detection in a single cell to 60% of cells4,5</td>
 </tr>
 </tbody>
</table>
A clear definition of a high-risk diagnosis is needed

<h2>Response rates and survival outcomes are lower for patients with genetic abnormalities versus those with standard risk cytogenetics2,17</h2>

<h3>The presence of multiple cytogenetic abnormalities further decreases prognosis compared with individual high-risk abnormalities1,18,19</h3>

<h3>There remains a detrimental gap between high-risk and standard risk cytogenic patients5,7 
 &nbsp;</h3>

Multiple Myeloma: High Risk Cytogenetics

<h2>Multiple myeloma in older adults</h2>

<table border="1" cellpadding="1" cellspacing="1" style="width: 100%;">
 <tbody>
 <tr>
 <td>
 Multiple myeloma is predominantly a disease of the elderly1</td>
 </tr>
 </tbody>
</table>
<table border="1" cellpadding="1" cellspacing="1" style="width: 100%;">
 <tbody>
 <tr>
 <td>
 Median age at diagnosis 68 years2*</td>
 </tr>
 </tbody>
</table>
Elderly/frail patients have fewer treatment options than younger patients3,4
*2014 EU data

<h2>Patients &gt;65 years of age have worse survival rates than younger patients1</h2>

Characteristics commonly found in elderly patients make treatment di cult1,4-6

Common symptoms can all be attributed to other etiologies in elderly patients
Difficulty of diagnosis in elderly patients3

<table border="1" cellpadding="1" cellspacing="1" style="width: 100%;">
 <tbody>
 <tr>
 <td>
 50%&nbsp;of patients need 3 GP visits before diagnosis</td>
 </tr>
 </tbody>
</table>
<table border="1" cellpadding="1" cellspacing="1" style="width: 100%;">
 <tbody>
 <tr>
 <td>
 Average delay in diagnosis:&nbsp;6 MONTHS</td>
 </tr>
 </tbody>
</table>

There is an unmet medical need in this di cult-to-treat patient population

Multiple Myeloma: Elderly Patients

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